Category Archives: Breast Cancer

Mastectomies to Prevent Cancer

Diana Zuckerman, PhD, Cancer Prevention and Treatment Fund

Every year, thousands of women choose to undergo a mastectomy when lumpectomy would be an equally effective option for them. Some women choose a bilateral mastectomy when there is cancer in only one breast. Even women who do not have breast cancer may undergo mastectomies as a preventive measure because of their high risk of breast cancer.

Helping patients make an informed decision about whether to have a mastectomy is an important aspect of the physician-patient relationship. Unfortunately, many patients are not able to get the information they need from their physicians. A patient who is seriously considering a mastectomy or bilateral mastectomy that is not medically necessary may be basing her decision more on fear than on information. They may benefit from unbiased information, counseling, or from a second opinion before making a final decision.

The purpose of this article is to provide information that patients and family members can use to help them discuss their options with their physicians.

Gene Mutations that Increase the Risk of Breast Cancer (BRCA1 and BRCA2)

Women with known mutations in the BRCA1 and BRCA2 genes have a lifetime risk of breast cancer ranging from 40% to 85%, compared to 12% for women in the general population.1 Women with BRCA1 or BRCA2 mutations often develop breast cancer before age 50 and have a high risk of bilateral breast cancer and ovarian cancer.2 Removing breasts with no sign of cancer is called a prophylactic (preventive) mastectomy. Prophylactic mastectomy and prophylactic oophorectomy (removal of the ovaries) have both been shown to greatly reduce—but not eliminate—the risk of breast cancer in BRCA mutation carriers.1

Among women with strong family histories of breast cancer, individuals of Ashkenazi Jewish descent have an 8 times greater frequency of carrying these mutations in BRCA1 or BRCA2 compared with other women.3

Lumpectomy with radiation therapy is just as effective for preventing in-breast tumor recurrence in patients with BRCA mutations as it is for other women. Questions remain, however, about how other adjuvant treatments (such as chemotherapy) affect survival of women with these gene mutations.4

For women with the BRCA1 or BRCA2 genes, it is important to remember that the risk of breast cancer in the next 5 or 10 years is much lower than the lifetime risk of breast cancer. For example, the risk of breast cancer in her 20’s is very low, even with BRCA1 (less than 3%) or BRCA2 (approximately 1%). For a 30-year old woman, the risk by age 39 is higher (10% for women with BRCA1 and 8% for BRCA2). For a 40-year-old woman, the risk by age 49 is 16% for women with BRCA1 and 13% for women with BRCA2.3 Although these 10-year risk levels are much higher than for most women, they are much lower than the life-time risk that is so frightening. It is also important to remember that cancer treatments and prevention strategies are improving, so the risks of cancer may decrease and the survival rates are improving.

Non-Surgical Alternatives to Prophylactic Mastectomies

Many women who are at high risk for breast cancer consider having a prophylactic mastectomy to reduce their future cancer risk. Prophylactic mastectomies can prevent breast cancer, but many women who undergo prophylactic mastectomies would never have developed breast cancer, even without the surgery.

This is a decision that women need to make for themselves, but to make that decision they need a clear understanding of the risks and benefits as well as alternative strategies that also reduce risk.

Tamoxifen and raloxifene have both been shown to reduce the risk of breast cancer for women who have not had cancer but are at greater risk. However, it is not yet known if these drugs can prevent breast cancer for women with BRCA1 or BRCA2 mutations.

For women at high risk of breast cancer for any reason, mammography screening at a young age and annual breast MRIs are alternatives to prophylactic mastectomy. MRIs are more accurate than mammograms for young women and women with dense breast tissue.

Research indicates that a low-fat diet, weight control, and exercise may reduce the risk of breast cancer for all women, including women at high risk and women who previously were treated for breast cancer.4, 5

All articles are reviewed and approved by Diana Zuckerman, PhD, and other senior staff.

References

1 Schrag D, Kuntz KM, Garber JE, Weeks JC. Decision analysis – effects of prophylactic mastectomy and oophorectomy on life expectancy among women with BRCA1 or BRCA2 mutations. New England Journal of Medicine. 1997;337(6):434.

2 Rubinstein, WS. Hereditary breast cancer in Jews. Familial Cancer. 2004;3:249-257.

3 Chen S, Iversen ES, Friebel T, Finkelstein D, Weber BL, Eisen A. et al. Characterization of BRCA 1 and BRCA 2 mutations in a large United States sample. Journal of Clinical Oncology. 2006;24(6):863-869.

4 Breast Cancer (PDQ®): Treatment. National Cancer Institute. http://www.cancer.gov/cancertopics/pdq/treatment/breast/HealthProfessional/

5 Prentice RL, Caan B, Chlebowski RT, Patterson R, Kuller LH, Ockene JK, et al., The women’s health initiative randomized controlled dietary modification trial. JAMA. 2006;295(6):629-642

Hormonal Therapy for Post-menopausal Women with Early Stage Breast Cancer

Anna Mazzucco, PhD, Brandel France de Bravo, MPH, Caroline Halsted, Danielle Shapiro, MD, MPH, and Diana Zuckerman, PhD, Cancer Prevention and Treatment Fund

Breast cancer is the most common type of cancer in women around the world, and the second leading cause of cancer deaths among U.S. women. The survival rate for early-stage breast cancer is very high.  For women whose cancer is diagnosed when it is only in the breast, the 5-year survival rate is 99%.  For women whose breast cancer has spread to the lymph nodes, the 5-year survival rate is 85%.

Women who are diagnosed with early-stage breast cancer almost always undergo surgery to remove the cancer (either lumpectomy/partial mastectomy or mastectomy). Most will also choose at least one other treatment in addition to surgery:

1) If they have a lumpectomy, they often undergo radiation to either shrink the tumor before surgery or to kill any cancer cells in the breast that were missed during surgery.

2) If their cancer is estrogen receptor positive (about 84% of breast cancers), many women will try to take hormonal therapy for at least five years after surgery to lower the chance of cancer coming back in either breast the future. For pre-menopausal women, the standard treatment is tamoxifen. For women who have completed menopause (post-menopausal breast cancer), tamoxifen and/or an aromatase inhibitor can be used.[1]

Types of Hormonal Therapies for Early-Stage Breast Cancers

Hormonal therapy (also called endocrine therapy or anti-estrogen therapy) is the opposite of the type of hormones women sometimes take to reduce the symptoms of menopause. It lowers your estrogen levels instead of increasing them.[1]

Hormonal therapy is recommended for most women with breast cancer, and sometimes it is taken by women who have not been diagnosed with breast cancer but are at high risk for it based on their genes or family history. When hormonal therapy is used before breast cancer develops, it is called “primary prevention” or “chemoprevention.” Chemoprevention is completely different from the drugs used in chemotherapy to treat breast cancer.[1]  See our article on breast cancer prevention.

Four types of hormonal therapy are FDA-approved for early-stage breast cancer treatment for post-menopausal women: tamoxifen, exemestane, letrozole, and anastrozole.[3]

For post-menopausal women, there are many recommended ways to take hormone therapy, including: [4]

  • Taking tamoxifen for 5 to 10 years
  • Taking an aromatase inhibitor for 5 to 10 years
  • Taking tamoxifen for 5 years, then switching to an aromatase inhibitor for the next 5 years
  • Taking tamoxifen for 2-3 years, then switching to an aromatase inhibitor for the next 5 years

How Does Hormonal Therapy Work?

Tamoxifen:

Tamoxifen is a selective estrogen receptor modulator (SERM), which means it blocks estrogen activity in breast tissue, but promotes estrogen activity in other tissues (such as in bone and the inner lining of the uterus). Tamoxifen is only effective in breast cancers that are estrogen receptor positive.[3,4]

Aromatase inhibitors:

In post-menopausal women, the ovaries slow down the production of estrogen, but the body uses an enzyme called aromatase to make estrogen from other hormones. Aromatase inhibitors block aromatase, which lowers the amount of estrogen in the body. By taking away the supply of estrogen, aromatase inhibitors help to stop the growth of cancer cells.[3,4]

How Effective are the Treatments?

The effectiveness of treatments is often reported in terms of risk or risk reduction. Risk is another word for chance–what is the chance that something will happen, such as cancer returning or the patient dying? Risk can be reported in terms of relative risk or absolute risk. Let’s use simple numbers to show what we mean: In a study 100 women are given a new drug and 100 other women are given an older drug.  What if the study showed that 4 patients (4%) taking the older drug became nauseous compared to only 2 patients (2%) taking the new drug.  The relative risk of patients getting nauseous is 50% lower for patients taking the new drug, and that sounds impressive.  But the absolute difference is only 2% – when you subtract 2% taking the new drug compared to 4% taking the old drug.

Based on the statistics, the odds may favor taking the new drug. But if the new drug costs much more or has other side effects, a patient might decide she is willing to take the 2% greater risk of becoming nauseous. We prefer to use the absolute difference in risk as it is more informative for patients than the relative risk.

Tamoxifen

Over decades of clinical trials in hundreds of thousands of women, tamoxifen has been shown to reduce the chances of breast cancer recurrence and breast cancer death. But it is important to consider exactly what the benefits are likely to be for you.

Breast cancer recurrence:

A landmark report showed that about 23% of women aged 55 and older who took tamoxifen for 5 years after their cancer was removed had a breast cancer recurrence within 10 years compared to about 42% of women 55-69 and 44% of women 70 and older who did not take tamoxifen.  In that study, women with early-stage breast cancer included women with Stage 1, Stage 2, and Stage 3A; in other words, it ranges from a very tiny breast cancer to a large cancer that has spread to several lymph nodes. The researchers defined breast cancer recurrence as the first appearance of any breast cancer including, cancer in the same breast, cancer in the opposite breast, or distant spread of cancer.[6]

Breast cancer deaths

Among women who were 55-69 years old at the time of diagnosis, about 90% who did not have a breast cancer recurrence were alive for at least 10 years, regardless of whether they took tamoxifen or not. For women in that age group, about 16% of women who took tamoxifen and had a recurrence died from breast cancer within 10 years of the initial diagnosis, compared to 26% of women who did not take tamoxifen and had a recurrence.[6]

Among women who were 70 years old or more at the time of their diagnosis and did not have a breast cancer recurrence, 80% who took tamoxifen were alive 10 years later, compared to 70% of women who did not take tamoxifen. Importantly, this difference was not statistically significant, meaning it could have happened by chance and is unlikely to be related to tamoxifen therapy.  Among women in this age group who had a breast cancer recurrence, about 20% who took tamoxifen and had a recurrence died from breast cancer within 10 years of the initial diagnosis compared to 37% of women who did not take tamoxifen and had a recurrence. [6]

Living Longer

Most women who are diagnosed with breast cancer do not die from breast cancer.  Of course, eventually they die of something else.  For women who were 55-69 years old at the time of their diagnosis, 5 years of tamoxifen helped women live longer.  More than 90% of women who did not have a breast cancer recurrence were alive 10 years later, regardless of whether they took tamoxifen or not. In contrast, about 76% of women who took tamoxifen and had a breast cancer recurrence were alive 10 years after the initial diagnosis, compared to 67% of women who did not take tamoxifen.[6]

By the time women are over 70, they are likely to have health issues whether or not they are diagnosed with breast cancer. Among those who did not have a breast cancer recurrence, about 80% of women taking tamoxifen and 70% of women not taking tamoxifen were alive 10 years later.  However, this apparent 10% difference was not statistically significant and therefore is probably not related to tamoxifen. In contrast, among women who had a recurrence, about 67% of women who took tamoxifen were alive 10 years later compared to 47% of women who did not take tamoxifen.[6]

As you can see, the benefits of tamoxifen depend on how old and healthy a woman is when she is diagnosed In addition, certain characteristics of early-stage breast cancers, including size of the tumor, types of cancer cells, and how many lymph nodes the cancer had spread to prior to surgery, can help doctors predict the chances of breast cancer recurrence. Therefore, it is important for you to talk with your doctor about these specific issues and which treatment options may be right for you.  Remember that some benefits (such as survival) might be more important to you than others (such as recurrence) – or not!

Aromatase Inhibitors:

Aromatase inhibitors have also been shown to benefit post-menopausal breast cancer patients.  An international breast cancer study showed that about 84% of women taking letrozole were alive and cancer free at 5 years compared to about 81% of women taking tamoxifen. Despite the difference in dying from breast cancer, however, there was no difference in terms of the percentage of women who were alive 5 years after diagnosis.

The benefits of aromatase inhibitors continued 10 years after diagnosis, with about 19% of women who took letrozole having any cancer recurrence compared to about 23% of women who took tamoxifen. Breast cancer recurrence included any breast cancer in the same breast, the opposite breast, or distant spread of cancer.[3]

When considering your treatment options, talk with your doctor about your overall health and your heart health, because all women (including women with breast cancer) are more likely to die from heart disease than breast cancer. And some treatments for breast cancer can harm your heart. Read more about heart health and breast cancer in our article.

Treatment Considerations

There are many ways to take hormone therapy, including switching between the types of therapy, and taking the hormone therapy for additional years. The choices can be confusing. Here are some questions to think about: 

What are the benefits of extending therapy? Studies show that extending therapy after an initial 5-year period can lower a woman’s chances of cancer recurrence (including any breast cancer in the same breast, the opposite breast, or distant spread) by a small, but statistically significant 2% to 4%. The study looked at different hormone regimens including “primary” AI (AI for 5 years), “sequential” AI (tamoxifen for 2 years followed by 3 years of AI), and extended AI (5 years of AI after 5 years of tamoxifen). For example, about 7% to 12% of women who took any hormone therapy for 5 years had a recurrence compared to 5% to 8% of women who extended their therapy.[10]

For how long should women extend therapy? A 2018 study found that women adding on 2.5 extra years of letrozole had the same chances of surviving without their breast cancer returning as women adding letrozole for 5 years. However, about 1% of women who took letrozole for an extra 5 years had a new breast cancer develop in the opposite breast compared to 3% in the 2.5 year group. That difference is small but it is a way to lower your already small risk of developing a new cancer in your other breast and making it even smaller.[11,12]

As you consider your treatment options,  it is important to consider the risks as well, as described later in the next section of this article.

Side Effects and Risks of Treatment

Tamoxifen increases the chances of a woman developing endometrial cancer and blood clots in legs and lungs, especially for women over 50 years of age.[3,16] Women taking tamoxifen are also more likely to develop endometrial cancer, although the overall risk is still low; about 2 women out of 1,000 taking tamoxifen will get endometrial cancer each year.[16] In a Danish study, the 5-year risk of developing blood clots was about 1.2% in women with breast cancer taking tamoxifen compared to 0.5% in women with breast cancer who were not taking tamoxifen. Moreover, tamoxifen therapy often causes side effects similar to those experienced in menopause, including hot flashes and irregular periods.[16] In one study, 41% of women taking tamoxifen experienced hot flashes, and 10% experienced abnormal vaginal bleeding.[19]

Aromatase inhibitors increase the risk for osteoporosis compared with tamoxifen or taking no hormonal therapy at all.  Exemestane, a commonly used aromatase inhibitor (brand name Aromasin), also increases the risk for visual disturbances, allergic reaction, or diarrhea.  In one study, about 36% of women experienced joint problems while taking anastrozole, (brand name Arimidex) compared to about 30% of women taking tamoxifen.

The most common complications from hormonal therapy are listed above.  In addition, in very rare cases, other side effects of hormonal therapy can be fatal or can harm a patient’s quality of life.  Close monitoring of women for symptoms, such as abnormal uterine bleeding, is needed, and women taking tamoxifen should receive annual pelvic exams.[3]

Different women respond differently to the various forms of hormonal therapy, which is why it is not uncommon for women to switch to different hormonal treatments after starting.

The Bottom Line

There are many ways to treat early-stage breast cancer in post-menopausal women, in addition to surgery. A woman’s age, tumor characteristics, overall health, and personal wishes/goals may impact her decision. Talk with your doctor about which treatment options may be right for you by asking about the exact benefits of specific treatments on recurrence and overall survival, and considering these specific issues and not just what is best for cancer patients on average.

Footnotes:

  1. American Cancer Society. Cancer Treatment and Survivorship: Facts and Figures 2016-2017. Available online: https://www.cancer.org
  2. Burstein HJ. et al. Adjuvant Endocrine Therapy for Women With Hormone Receptor–Positive Breast Cancer: American Society of Clinical Oncology Clinical Practice Guideline Update on Ovarian Suppression. Journal of Clinical Oncology. 2017;34(14): 1689-1701. Doi: 1200/JCO.2015.65.9573
  3. National Cancer Institute. Breast Cancer Treatment (PDQ). (Nov. 2017). Available online: https://www.cancer.gov/types/breast/patient/breast-treatment-pdq#section/_125
  4. Adjuvant Therapy for Breast Cancer. (Aug. 2017). Available online: https://emedicine.medscape.com/article/1946040-overview#showall
  5. Colleoni M. et al. Annual Hazard Rates of Recurrence for Breast Cancer During 24 Years of Follow-Up: Results From the International Breast Cancer Study Group Trials I to V. J Clin Oncol. 2016;34(9): 927-935. doi: 1200/JCO.2015.62.3504
  6. Early Breast Cancer Trialists’ Collaborative Group (EBCTCG). Relevance of breast cancer hormone receptors and other factors to the efficacy of adjuvant tamoxifen: patient-level meta-analysis of randomised trials. Lancet. 2011;378(9793): 771-784. doi:1016/S0140-6736(11)60993-8
  7. Gierach GL, Curtis RE, Pfeiffer RM, et al. Association of Adjuvant Tamoxifen and Aromatase Inhibitor Therapy With Contralateral Breast Cancer Risk Among US Women With Breast Cancer in a General Community Setting. JAMA Oncol. 2017;3(2): 186–193. doi:1001/jamaoncol.2016.3340
  8. Early Breast Cancer Trialists’ Collaborative Group (EBCTCG). Aromatase inhibitors versus tamoxifen in early breast cancer: patient-level meta-analysis of the randomised trials. Lancet. 2015;386(10001): 1341 – 1352. doi: http://dx.doi.org/10.1016/S0140-6736(15)61074-1
  9. Pohlmann PR and Isaacs C. Extended Adjuvant Endocrine Therapy for Postmenopausal Women: Treating Many to Benefit a Few, JNCI: Journal of the National Cancer Institute. 2018;110(1): djx142, doi: https://doi.org/10.1093/jnci/djx142
  10. Burstein HJ, Prestrud AA, Seidenfeld J, et al. American Society of Clinical Oncology Clinical Practice Guideline: Update on Adjuvant Endocrine Therapy for Women With Hormone Receptor–Positive Breast Cancer. Journal of Clinical Oncology. 2010;28(23):3784-3796. doi:10.1200/JCO.2009.26.3756.
  11. Blok EJ, et al. Optimal Duration of Extended Adjuvant Endocrine Therapy for Early Breast Cancer; Results of the IDEAL Trial (BOOG 2006-05). JNCI: Journal of the National Cancer Institute. 2018; 110(1): djx134, https://doi.org/10.1093/jnci/djx134
  12. Van de Velde, C.J.H. et al. Optimal duration of extended letrozole treatment after 5 years of adjuvant endocrine therapy; results of the randomized phase III IDEAL trial (BOOG 2006–05). European Journal of Cancer. 2017;72(Supp1):S9. doi: http://dx.doi.org/10.1016/S0959-8049(17)30108-9
  13. Gianni L. et al. Treatment with trastuzumab for 1 year after adjuvant chemotherapy in patients with HER2-positive early breast cancer: a 4-year follow-up of a randomised controlled trial. Lancet Oncology. 2011;12(3): 236-44. doi: https://doi.org/10.1016/S1470-2045(11)70033-X
  14. Cameron D. et al. 11 years’ follow-up of trastuzumab after adjuvant chemotherapy in HER2-positive early breast cancer: final analysis of the HERceptin Adjuvant (HERA) trial. Lancet. 2017;389(10075): 1195-1205. doi: https://doi.org/10.1016/S0140-6736(16)32616-2
  15. Stenger M. ASCO Post: 11-Year Follow-up of Adjuvant Trastuzumab in the HERA Trial. (March 2017). Available online: http://www.ascopost.com/News/48405
  16. Gogas H, Markopoulos C, Blamey R. Should women be advised to take prophylactic endocrine treatment outside of a clinical trial setting? Ann Oncol. 2005;16:1861-1866. Available online: https://watermark.silverchair.com
  17. Fisher B, et al. J Natl Cancer Inst. 1994; 86:527-537.
  18. Bonneterre, et al. J Clin Oncol. 2000; 18:3748-3757.
  19. Howell A, et al. Results of the ATAC (Arimidex, Tamoxifen, Alone or in Combination) trial after completion of 5 years’ adjuvant treatment for breast cancer. Lancet. 2005;365(9453): 60-2. doi: 1016/S0140-6736(04)17666-6
  20. Bliss JM. et al. Disease-Related Outcomes With Long-Term Follow-Up: An Updated Analysis of the Intergroup Exemestane Study. Journal of Clinical Oncology. 2012;30(7): 709-717. doi: 1200/JCO.2010.33.7899
  21. Drugs and Diseases: Gosarelin. Available online: https://reference.medscape.com/drug/zoladex-la-goserelin-342129
  22. Drugs and Diseases: Trastuzumab. Available online: https://reference.medscape.com/drug/herceptin-ogivri-trastuzumab-342231#5

Hormonal Therapy for Pre-menopausal Women with Early Stage Breast Cancer

Anna Mazzucco, PhD, Brandel France de Bravo, MPH, Caroline Halsted, Danielle Shapiro, MD, MPH, and Diana Zuckerman, PhD, Cancer Prevention and Treatment Fund

Breast cancer is the most common type of cancer in women around the world, and the second leading cause of cancer deaths among U.S. women. The survival rate for early-stage breast cancer is very high.  For women whose breast cancer is diagnosed before it has spread, the 5-year survival rate is 99%.  For women whose breast cancer has spread to the lymph nodes, the 5-year survival rate is 85%.

Women who are diagnosed with early-stage breast cancer almost always undergo surgery to remove the cancer (either lumpectomy/partial mastectomy or mastectomy). Most will also choose at least one other treatment in addition to surgery:

1) If they have a lumpectomy, they often undergo radiation either to shrink the tumor before surgery or to kill any cancer cells in the breast that were missed during surgery.

2) If their cancer is estrogen receptor positive (about 84% of breast cancers), many women will try to take hormonal therapy for at least five years after surgery to lower the chance of cancer in either breast in the future. For pre-menopausal women, the standard treatment is tamoxifen.[1]

Types of Hormonal Therapies for Early Stage Breast Cancer

Hormonal therapy (also called endocrine therapy or anti-estrogen therapy) is the opposite of the type of hormones women sometimes take to reduce the symptoms of menopause. It lowers your estrogen levels instead of increasing them.[1]

Hormonal therapy is recommended for most women with breast cancer, and sometimes it is taken by women who have not been diagnosed with breast cancer but are at high risk for it based on their genes or family history. When hormonal therapy is used before breast cancer develops, it is called “primary prevention” or “chemoprevention.” Chemoprevention is completely different from the drugs used in chemotherapy to treat breast cancer.[1] See our article on breast cancer prevention.

How Does Hormonal Therapy Work?

Tamoxifen is a selective estrogen receptor modulator (SERM), which means it blocks estrogen in breast tissue, but promotes it in other tissues (such as in bone and the inner lining of the uterus). Tamoxifen is only effective in breast cancers that are estrogen receptor positive.[3,4]

How Effective Are the Treatments?

The effectiveness of treatments is often reported in terms of risk or risk reduction. Risk is another word for chance–what is the chance that something will happen, such as cancer returning or the patient dying? Risk can be reported in terms of relative risk or absolute risk. Let’s use simple numbers to show what we mean: In a study, 100 women are given a new drug and 100 other women are given an older drug.  What if the study showed that 4 patients (4%) taking the older drug became nauseous compared to only 2 patients (2%) taking the new drug.  The relative risk of patients getting nauseous is 50% lower for patients taking the new drug, and that sounds impressive. But the absolute difference is only 2% — when you subtract 2% taking the new drug compared to 4% taking the old drug.

Based on the statistics, the odds may favor taking the new drug. But if the new drug costs much more or has other side effects, a patient might decide she is willing to take the 2% greater risk of becoming nauseous. We prefer to focus on the absolute difference in risk as it is more informative for patients than the relative risk.

Tamoxifen therapy after surgery for early-stage breast cancer reduces the chances of breast cancer returning and the chances of dying from breast cancer.  But it is important to consider exactly what the benefits are likely to be for you.

Benefits of 5-Year Therapy

Does tamoxifen prevent breast cancer recurrence?

A landmark report showed that about 26% of women taking tamoxifen for 5 years after their cancer was removed had a breast cancer recurrence within 10 years, compared to about 40% of women not taking tamoxifen.[6] In that study, women with early-stage breast cancer includes women with Stage 1, Stage 2, and Stage 3A; in other words, it ranges from a very tiny breast cancer to a large cancer that has spread to several lymph nodes.  The researchers defined breast cancer recurrence as the first appearance of any breast cancer including, cancer in the same breast, cancer in the opposite breast, or distant spread of cancer. However, women who took tamoxifen for 5 years had a 0.6% chance per year of having their breast cancer return in the same breast (this is called local recurrence) compared to a 1.1% chance per year in women who did not take tamoxifen.

Does tamoxifen prevent breast cancer deaths in women with breast cancer recurrence?

Most  women who had a recurrence did not die of breast cancer:  About 17% of women younger than 45 years and 22% of women aged 45-54 years who took tamoxifen died from breast cancer within 10 years of the initial diagnosis, compared to, respectively,  20% and 28% of women those same ages who did not take tamoxifen.[6]

Does tamoxifen save lives?

The benefits of tamoxifen vary depending on  certain characteristics of early-stage breast cancers, including size of the tumor, types of cancer cells, and how many lymph nodes the cancer had spread to prior to surgery.  These issues can help doctors predict the chances of breast cancer recurrence.  Therefore, it is important for you to talk with your doctor about these specific issues and which treatment options may be right for you.  Remember that some benefits (such as survival) might be more important to you than others (such as recurrence) – or not!

Preventing Breast Cancer in the Opposite Breast

About 1 in 20 (5%) women diagnosed with breast cancer will develop breast cancer in the opposite breast within the 10 years after first breast cancer diagnosis. A 2017 study in the prestigious medical journal JAMA found that taking tamoxifen can reduce the percentage of those women from developing cancer in the opposite breast within 10 years, from about 5% to  2%.[7] Unfortunately, the study authors did not report on breast cancer deaths or deaths for any other reason. Therefore, we do not know whether tamoxifen’s reduction of cancer in the opposite breast had any impact on the women’s longevity.

Benefits of Extending Therapy

One popular option is to change from tamoxifen to an aromatase inhibitor when menopause is reached (menopause occurs when a woman has not had a menstrual period for a continuous 12 months).  Read more about aromatase inhibitors in our article on post-menopausal early stage breast cancer.

Extending tamoxifen for an additional 5 years can also decrease a woman’s chances of breast cancer recurrence by about 4% in the 10 years after surgery if her cancer had spread to her lymph nodes prior to surgery.[2]  However, women who had early-stage breast cancer that did not spread to their lymph nodes did not benefit from more than 5 years of tamoxifen.[2]

In addition to reducing recurrence, the studies also found that taking tamoxifen for 10 years instead of 5 years reduced the chances of dying from breast cancer within those 10 years from about 15% to about 12%. These differences are small and disappear for women with the earliest stage breast cancers. Even more important, overall survival –how long a woman lives after her initial diagnosis of breast cancer–was not significantly affected by taking tamoxifen for more than 5 years.[2]  In other words, even if a woman taking tamoxifen for 10 years was less likely to die of breast cancer within those 10 years, she was not less likely to die from any cause.

When considering your treatment options, talk with your doctor about your overall health and your heart health, because all women (including women with breast cancer) are more likely to die from heart disease than breast cancer. And some treatments for breast cancer can harm your heart.  Read more about heart health and breast cancer in our article.

Side Effects and Risks of Treatment

Tamoxifen increases the chances of developing endometrial cancer and blood clots in the legs and lungs.[3,16] In a Danish study, the 5-year risk of developing blood clots was about 1.2% in breast cancer patients taking tamoxifen compared to 0.5% in breast cancer patients who were not taking tamoxifen.[10]  Tamoxifen often causes side effects similar to those experienced in menopause, including hot flashes and irregular periods.[16] In one study, 41% of women taking tamoxifen experienced hot flashes, and 10% experienced abnormal periods .[19]

The Bottom Line

There are many ways to treat early-stage breast cancer in pre-menopausal women, in addition to surgery. A woman’s age, tumor characteristics, and personal wishes/goals may affect the benefits and risks of different treatments. Talk with your doctor about which treatment options may be right for you by asking about the exact benefits of specific treatments on recurrence and overall survival, and considering these specific issues and not just what is best for cancer patients on average.

Footnotes:

  1. American Cancer Society. Cancer Treatment and Survivorship: Facts and Figures 2016-2017. Available online: https://www.cancer.org
  2. Burstein HJ. et al. Adjuvant Endocrine Therapy for Women With Hormone Receptor–Positive Breast Cancer: American Society of Clinical Oncology Clinical Practice Guideline Update on Ovarian Suppression. Journal of Clinical Oncology. 2017;34(14): 1689-1701. Doi: 1200/JCO.2015.65.9573
  3. National Cancer Institute. Breast Cancer Treatment (PDQ). (Nov. 2017). Available online: https://www.cancer.gov/types/breast/patient/breast-treatment-pdq#section/_125
  4. Adjuvant Therapy for Breast Cancer. (Aug. 2017). Available online: https://emedicine.medscape.com/article/1946040-overview#showall
  5. Colleoni M. et al. Annual Hazard Rates of Recurrence for Breast Cancer During 24 Years of Follow-Up: Results From the International Breast Cancer Study Group Trials I to V. J Clin Oncol. 2016;34(9): 927-935. doi: 1200/JCO.2015.62.3504
  6. Early Breast Cancer Trialists’ Collaborative Group (EBCTCG). Relevance of breast cancer hormone receptors and other factors to the efficacy of adjuvant tamoxifen: patient-level meta-analysis of randomised trials. Lancet. 2011;378(9793): 771-784. doi:1016/S0140-6736(11)60993-8
  7. Gierach GL, Curtis RE, Pfeiffer RM, et al. Association of Adjuvant Tamoxifen and Aromatase Inhibitor Therapy With Contralateral Breast Cancer Risk Among US Women With Breast Cancer in a General Community Setting. JAMA Oncol. 2017;3(2): 186–193. doi:1001/jamaoncol.2016.3340
  8. Early Breast Cancer Trialists’ Collaborative Group (EBCTCG). Aromatase inhibitors versus tamoxifen in early breast cancer: patient-level meta-analysis of the randomised trials. Lancet. 2015;386(10001): 1341 – 1352. doi: http://dx.doi.org/10.1016/S0140-6736(15)61074-1
  9. Pohlmann PR and Isaacs C. Extended Adjuvant Endocrine Therapy for Postmenopausal Women: Treating Many to Benefit a Few, JNCI: Journal of the National Cancer Institute. 2018;110(1): djx142, doi: https://doi.org/10.1093/jnci/djx142
  10. Burstein HJ, Prestrud AA, Seidenfeld J, et al. American Society of Clinical Oncology Clinical Practice Guideline: Update on Adjuvant Endocrine Therapy for Women With Hormone Receptor–Positive Breast Cancer. Journal of Clinical Oncology. 2010;28(23):3784-3796. doi:10.1200/JCO.2009.26.3756.
  11. Blok EJ, et al. Optimal Duration of Extended Adjuvant Endocrine Therapy for Early Breast Cancer; Results of the IDEAL Trial (BOOG 2006-05). JNCI: Journal of the National Cancer Institute. 2018; 110(1): djx134, https://doi.org/10.1093/jnci/djx134
  12. Van de Velde, C.J.H. et al. Optimal duration of extended letrozole treatment after 5 years of adjuvant endocrine therapy; results of the randomized phase III IDEAL trial (BOOG 2006–05). European Journal of Cancer. 2017;72(Supp1):S9. doi: http://dx.doi.org/10.1016/S0959-8049(17)30108-9
  13. Gianni L. et al. Treatment with trastuzumab for 1 year after adjuvant chemotherapy in patients with HER2-positive early breast cancer: a 4-year follow-up of a randomised controlled trial. Lancet Oncology. 2011;12(3): 236-44. doi: https://doi.org/10.1016/S1470-2045(11)70033-X
  14. Cameron D. et al. 11 years’ follow-up of trastuzumab after adjuvant chemotherapy in HER2-positive early breast cancer: final analysis of the HERceptin Adjuvant (HERA) trial. Lancet. 2017;389(10075): 1195-1205. doi: https://doi.org/10.1016/S0140-6736(16)32616-2
  15. Stenger M. ASCO Post: 11-Year Follow-up of Adjuvant Trastuzumab in the HERA Trial. (March 2017). Available online: http://www.ascopost.com/News/48405
  16. Gogas H, Markopoulos C, Blamey R. Should women be advised to take prophylactic endocrine treatment outside of a clinical trial setting? Ann Oncol. 2005;16:1861-1866. Available online: https://watermark.silverchair.com
  17. Fisher B, et al. J Natl Cancer Inst. 1994; 86:527-537.
  18. Bonneterre, et al. J Clin Oncol. 2000; 18:3748-3757.
  19. Howell A, et al. Results of the ATAC (Arimidex, Tamoxifen, Alone or in Combination) trial after completion of 5 years’ adjuvant treatment for breast cancer. Lancet. 2005;365(9453): 60-2. doi: 1016/S0140-6736(04)17666-6
  20. Bliss JM. et al. Disease-Related Outcomes With Long-Term Follow-Up: An Updated Analysis of the Intergroup Exemestane Study. Journal of Clinical Oncology. 2012;30(7): 709-717. doi: 1200/JCO.2010.33.7899
  21. Drugs and Diseases: Gosarelin. Available online: https://reference.medscape.com/drug/zoladex-la-goserelin-342129
  22. Drugs and Diseases: Trastuzumab. Available online: https://reference.medscape.com/drug/herceptin-ogivri-trastuzumab-342231#5

 

Ovarian Suppression Therapy for Young, Pre-Menopausal Women with Early-Stage Breast Cancer

Danielle Shapiro, MD, MPH, Cancer Prevention and Treatment Fund

Breast cancer is the most common type of cancer in women around the world, and the second leading cause of cancer deaths among U.S. women.

Women who are diagnosed with early-stage breast cancer almost always undergo surgery to remove the cancer (either lumpectomy/partial mastectomy or mastectomy). Most will also choose at least one other treatment in addition to surgery.

If their cancer is estrogen receptor positive (about 84% of breast cancers), many women will try to take hormonal therapy for at least five years after surgery to lower the chances of cancer coming back in the future.[1]

For pre-menopausal women younger than 35-40 years old who have estrogen receptor-positive cancer, ovarian suppression therapy may be considered. Ovarian suppression can be permanent (surgery) or temporary (medication), and it stops the body from making hormones.

Suppression therapy is sometimes recommended for women with stage 1 or 2 breast cancer who have high chance of the cancer returning, but more often recommended in women with stage 2 or 3 breast cancer who would ordinarily need chemotherapy. Suppression therapy is given in addition to tamoxifen or an aromatase inhibitor, and instead of or after chemotherapy.[2]

How Does Ovarian Suppression Therapy Work?

Ovarian suppression stops the ovaries from making hormones, which stops women from having menstrual cycles. It should only be used in women who are pre-menopausal and at high risk for cancer recurrence.

There are 3 types of ovarian suppression: 1) monthly hormone injections (temporary), 2) surgery to remove the ovaries (which results in irreversible menopause), and 3) radiation ablation therapy to remove the ovaries.[2]

How Effective is Ovarian Suppression Therapy?

A 2016 study found that 13% of women receiving both tamoxifen and ovarian suppression therapy died within 5 years of breast cancer compared to 15% receiving tamoxifen therapy only.  This is a very small difference, but was statistically significant, which means that it did not just happen by chance. For women who also received chemotherapy, 23% of patients receiving tamoxifen only died within 5 years, compared to 19% of women receiving tamoxifen plus ovarian suppression therapy.  Since women who undergo chemotherapy are those who are known to have a higher risk of dying from breast cancer, the researchers concluded that “high risk” women should be considered for ovarian suppression therapy.[2]

Women with stage I breast cancers who do not need chemotherapy and women who have small cancers (1 cm or less) without spread to lymph nodes should not receive ovarian suppression.[2]

Another study found that combining ovarian suppression with an aromatase inhibitor instead of with tamoxifen can decrease the chances of dying from breast cancer within 5 years, from 13% to 9%.[2]

Although women taking ovarian suppression therapy with hormone treatment were slightly less likely to die of breast cancer, they did not live longer than women who took hormone therapy alone.[2] In other words, they died of a different cause.

What Are the Potential Harms?

Ovarian Suppression therapy causes symptoms of menopause, because it stops the ovaries from making hormones. There are risks to removing the ovaries by surgery or radiation, such as the risks of anesthesia, infection, bleeding, and damage to nearby organs and tissues.

Removal of ovaries causes early menopause, so a young woman will no longer have periods or be able to get pregnant. Hormone injections can cause hot flashes or flushing, mood changes, depression, sexual dysfunction, and breast changes.

Serious side effects include blood clots, strokes, heart attacks, high or low blood pressure, and brittle or weak bones (osteoporosis).[3]

The Bottom Line

For young pre-menopausal women with estrogen-positive breast cancer, ovarian suppression therapy slightly reduces the chance of dying of breast cancer, but it doesn’t help women live longer. Because the therapy can be harmful with permanent side effects, young women should decide whether the small benefits outweigh the risks. Talk with your doctor about whether the risks outweigh the benefits for you.   

All articles are reviewed and approved by Dr. Diana Zuckerman and other senior staff.

References:

1. American Cancer Society. Cancer Treatment and Survivorship: Facts and Figures 2016-2017. Available online: https://www.cancer.org

2. Burstein HJ. et al. Adjuvant Endocrine Therapy for Women With Hormone Receptor–Positive Breast Cancer: American Society of Clinical Oncology Clinical Practice Guideline Update on Ovarian Suppression. Journal of Clinical Oncology. 2017;34(14): 1689-1701. Doi: 10.1200/JCO.2015.65.9573

3. Medscape. Drugs and Diseases: Gosarelin. Available online: https://reference.medscape.com/drug/zoladex-la-goserelin-342129

Targeted Therapy for Early-Stage Breast Cancer

Danielle Shapiro, MD, MPH, Cancer Prevention and Treatment Fund

Breast cancer is the most common type of cancer in women around the world, and the second leading cause of cancer deaths among U.S. women.

Women who are diagnosed with early-stage breast cancer almost always undergo surgery to remove the cancer (either lumpectomy/partial mastectomy or mastectomy). Most will also choose at least one other treatment in addition to surgery.

About 14% of all breast cancers (at all stages) make a protein called HER2. There are several targeted therapies that specifically stop the growth of these cancer cells. These therapies can be used with chemotherapy or hormonal therapy.[1]

How Does Targeted Therapy Work?

Trastuzumab targets breast cancer cells that make HER2, and stops them from growing.[2,3]

How Effective is Targeted Therapy?

Studies show that women with early-stage “HER2-positive” breast cancer may benefit from targeted therapy. The landmark study (called HERA) of this treatment showed that women taking trastuzumab for 1 year in addition to chemotherapy had a 21% chance of cancer returning compared to 28% for women getting chemotherapy alone.[4]

Overall survival refers to how long a woman lives after a diagnosis. For women diagnosed with early-stage HER2-positive breast cancer, 10.7% taking both trastuzumab and chemotherapy died within 4 years compared to 12.3% of women getting chemotherapy alone.  This is obviously a small benefit that would not help most women, but it could save the life of one or two women for every 100 receiving the targeted treatment.

At a 12-year follow up, the researchers found that taking trastuzumab for 2 years was not more beneficial than taking it for one year.[5,6]

What Are the Potential Harms?

Trastuzumab therapy can cause headaches, nausea, swelling, rash, and flu-like illness. In rare cases (less than 1%) trastuzumab can cause serious side effects including heart failure (a weakened heart), sudden difficulty breathing, low blood pressure, and sudden death. All women should have their hearts tested with a sonogram of the heart before deciding whether to take trastuzumab.  If they decide to take it, they should also have their hearts tested during treatment.[7]

In 2018, the American Heart Association recommended women with breast cancer discuss with their doctors their cardiovascular risks (such as family history, or having a diagnosis of diabetes, high blood pressure, or high cholesterol) and the risks of cancer therapies, including trastuzumab as well as many chemotherapy drugs, which can cause or worsen heart conditions. The damage to the heart continues after women have finished the therapies, and can be permanent. This risk to the heart helps explain why a treatment can help prevent breast cancer recurrence but have little benefit in terms of women living longer.[8]

The Bottom Line

For women with HER2-positive, early-stage breast cancer, targeted therapy may be beneficial. Because the therapy can be harmful to the heart, each woman needs to decide whether the benefits outweigh the risks for her. Talk with your doctor about your medical history and family history to decide which treatment options may be right for you.

All articles are reviewed and approved by Dr. Diana Zuckerman and other senior staff.

References:

  1. American Cancer Society. Cancer Treatment and Survivorship: Facts and Figures 2016-2017. Available online: https://www.cancer.org
  2. National Cancer Institute. Breast Cancer Treatment (PDQ). (Nov. 2017). Available online: https://www.cancer.gov/types/breast/patient/breast-treatment-pdq#section/_125
  3. Medscape. Adjuvant Therapy for Breast Cancer. (Aug. 2017). Available online: https://emedicine.medscape.com/article/1946040-overview#showall
  4. Gianni L. et al. Treatment with trastuzumab for 1 year after adjuvant chemotherapy in patients with HER2-positive early breast cancer: a 4-year follow-up of a randomised controlled trial. Lancet Oncology. 2011;12(3): 236-44. doi: https://doi.org/10.1016/S1470-2045(11)70033-X
  5. Cameron D. et al. 11 years’ follow-up of trastuzumab after adjuvant chemotherapy in HER2-positive early breast cancer: final analysis of the HERceptin Adjuvant (HERA) trial. Lancet. 2017;389(10075): 1195-1205. doi: https://doi.org/10.1016/S0140-6736(16)32616-2
  6. Stenger M. ASCO Post: 11-Year Follow-up of Adjuvant Trastuzumab in the HERA Trial. (March 2017). Available online: http://www.ascopost.com/News/48405
  7. Medscape. Drugs and Diseases: Trastuzumab. Available online: https://reference.medscape.com/drug/herceptin-ogivri-trastuzumab-342231#5
  8. Mehta LS. et al. Cardiovascular Disease and Breast Cancer: Where These Entities Intersect: A Scientific Statement From the American Heart Association. Circulation. 2018; (originally published February 1, 2018).https://doi.org/10.1161/CIR.0000000000000556

What are the Alternatives to Traditional Radiation Therapy for Breast Cancer?

Dana Casciotti, PhD, Anna E. Mazzucco, PhD, and Danielle Shapiro, MD, MPH, Cancer Prevention and Treatment Fund

Almost all women with early-stage breast cancer will live just as long if they choose lumpectomy (also called breast conserving surgery) instead of mastectomy. However, traditional radiation treatment is recommended for lumpectomy patients because it lowers their chances of the cancer returning.

Traditional radiation therapy is given on an outpatient basis 5 days each week for 6-8 weeks, and that is a difficult schedule for many patients. Many women living in rural areas or far from the hospital choose to get a mastectomy because daily radiation is so inconvenient.

For some women, radiation to a smaller area of the breast over a shorter period of time may be a useful alternative. These options are called partial breast irradiation (PBI).

PBI can be given with just 5-10 treatments over about a week’s time, and researchers are testing if treatments can be shortened to 2 days. According to experts, PBI can reduce the chances of a tumor coming back in the area around the lumpectomy from 10-25% to 3-4%.[1]

Based on a comprehensive 2016 research review, women who had PBI were more likely to have their tumor come back or to have a new tumor form in the same breast than women who had whole breast radiation treatment (WBRT). However, women who had PBI were not more likely to die any sooner or to later need a mastectomy.[2] 

PBI is not for everyone (see considerations below). Each type of PBI carries a different potential risk than the other types. For example, PBI with brachytherapy carries a higher risk of infection or seroma (fluid filled pocket in the breast tissue after surgery) than PBI with external beam radiation.[3] However, PBI with external beam radiation, increases risk for harmful effects to the lungs and heart. Three-dimensional models can reduce the radiation exposure to normal tissue, but do not completely eliminate risk.[4]

Across many studies, it is not clear whether PBI is more harmful to skin tissue than traditional radiation therapies.[5, 6,7] Harmful effects on the skin are rated on a scale of 1 to 4, with 4 being the worst. The changes in skin appearance include wrinkling, shrinkage, color change, red blotches, thickening, skin loss and destruction, etc.[8]  

PBI has been studied in clinical trials lasting no longer than 5 years, which isn’t really long enough to know if the therapy works the same or better than traditional radiation treatment. Traditional radiation therapy has been proven to be safe and effective for women for at least 15 years after treatment.

Who Should Consider PBI?

The American Society of Therapeutic Radiology and Oncology (ASTRO) provides the following recommendations: [9]

  1. Women aged 50 and over
  2. Early-stage breast cancer that is confined to one defined area of one breast only
  3. Estrogen receptor-positive breast cancer
  4. Women who had a breast lump removed with “clean margins” (no cancer cells were found in the area that was removed surrounding the lump)
  5. Women who did not have chemotherapy prior to surgery

Who should not be given PBI?

  1. Women aged 40 and younger
  2. Women who had the cancer removed but the margins contained cancer cells (“positive margins”)

What are the Types of PBI?

PBI can be given in the following ways:

  1. Intracavitary brachytherapy or MammoSite- A radiation bead is placed in the surgical cavity (the space left in the breast tissue after the breast lump is removed). This can be done at the time of surgery or later.
  2.  Interstitial brachytherapy- Several catheters are placed into the surgical cavity. Radioactive beads can be put in the breast through the catheters.
  3. Intra-operative technique- During the surgery, a machine is used that gives local radiation to the surgical cavity before the wound is closed.
  4. External beam radiotherapy using 3D modeling- Beams of radiation are given from different directions to match the 3D shape of the tumor. This focuses the rays on the tumor while reducing damage to the rest of the breast.

What are the Benefits and Harms of PBI?

Advantages of PBI:

  1. Smaller area of breast is given radiation, which reduces damage to normal breast tissue.
  2. Treatments can be given over days instead of weeks, making it more convenient and easier to schedule with other medical appointments.
  3. Because of the more convenient schedule, more women may be able to choose to get lumpectomy instead of mastectomy.

Disadvantages of PBI:

  1. Increased chances of tumor coming back or new tumor forming in the same breast compared to traditional radiation therapy.
  2. Because PBI can give a bigger dose of radiation, women may have later toxic effects, which affect the way the breast looks.
  3. Invasive approaches (placing beads in the surgical wound or catheters in the wound) can increase the chance of infection and can slow wound healing, which may affect the way the breast looks.

The Bottom Line

Radiation treatment can help women to conserve breast and prevent cancer spread after lumpectomy. PBI can be more convenient in the short run, but in the long run, we do not know if it is as safe or effective as traditional radiation treatment.

All articles are reviewed and approved by Dr. Diana Zuckerman and other senior staff.

References:
1. Kuznar, W. ASCO Reading Room: APBI: A Compromise Solution Following BCT–In low-risk breast cancer patients, recurrence rates equivalent to those for WBI. Medpage Today. (July 26, 2016). Available Online: https://www.medpagetoday.com/reading-room/asco/breast-cancer/59322?pop=0&ba=1&xid=tmd-md&hr=trendMD

2. Hickey BE, Lehman M, Francis DP, See AM. Partial breast irradiation for early breast cancer. Cochrane Database of Systematic Reviews 2016, Issue 7. DOI: 10.1002/14651858.CD007077.pub3.

3. Lei RY, Leonard CE, Howell KT, et al. Four-year clinical update from a prospective trial of accelerated partial breast intensity-modulated radiotherapy (APBIMRT). Breast Cancer Research and Treatment. 2013;140(1):119-133. doi:10.1007/s10549-013-2623-x.

4. Jacobson GM, Siochi RA. Low-Energy Intraoperative Radiation Therapy and Competing Risks of Local Control and Normal Tissue Toxicity. Frontiers in Oncology. 2017;7:212. doi:10.3389/fonc.2017.00212.

5. Whelan TJ, Olivotto I, Parpia S, et al. Interim toxicity results from RAPID: a randomized trial of accelerated partial breast irradiation (APBI) using 3D conformal external beam radiation therapy (3D CRT) Int J Radiat Oncol Biol Phys. 2013;85:21–22. DOI: 10.1200/JCO.2013.50.5511

6. Keshtgar MRS, Williams NR, Bulsara M, et al. Objective assessment of cosmetic outcome after targeted intraoperative radiotherapy in breast cancer: results from a randomized controlled trial. Breast Cancer Res Treat. 2013;140:519–525. DOI: 10.1007/s10549-013-2641-8.

7. Akhtari M, Abboud M, Szeja S, et al. Clinical outcomes, toxicity, and cosmesis in breast cancer patients with close skin spacing treated with accelerated partial breast irradiation (APBI) using multi-lumen/catheter applicators. Journal of Contemporary Brachytherapy. 2016;8(6):497-504. doi:10.5114/jcb.2016.64830.

8. RTOG Foundation. RTOG/EORTC Late Radiation Morbidity Scoring Schema. Available online: https://www.rtog.org/ResearchAssociates/AdverseEventReporting/RTOGEORTCLateRadiationMorbidityScoringSchema.aspx.

9. Correa C, et al. Accelerated Partial Breast Irradiation: Executive summary for the update of an ASTRO Evidence-based Consensus Statement. Practical Radiation Oncology 2017, Issue 7. DOI: 10.1016/j.prro.2016.09.007.

Drugs to Avoid for Women Taking Tamoxifen

Blossom Paravattil, Megan Cole, and Danielle Shapiro, MD, MPH, Cancer Prevention and Treatment Fund

The female hormone estrogen makes most cancer tumor cells grow and multiply. The drug tamoxifen was developed to block estrogen and therefore stop that growth, to help treat, prevent, and stop the recurrence of most breast cancer.  Breast cancer that is sensitive to estrogen is called “estrogen receptor-positive breast cancer.”

For tamoxifen to do its job, it needs to be broken down in the body by a key protein known as CYP2D6.  Unfortunately, many common medicines can block or slow down CYP2D6, and that would make tamoxifen less effective.

Certain medications used to treat depression should be avoided by women taking tamoxifen. The antidepressants paroxetine (Paxil) and fluoxetine (Prozac) have been found to increase women’s risk of dying of cancer if they are taking tamoxifen. Women who are on these medications should talk to their doctors about switching to other medicines that don’t affect how tamoxifen works.

The table below shows a list of drugs to avoid and alternative drugs that can be taken instead.

 

Classes of drugs Drugs that are likely to interfere with tamoxifen

Alternative drugs that should be safe to take with tamoxifen

Antidepressants (SSRI/SNRIs) Paxil, Prozac, Wellbutrin, and Cymbalta Effexor, Pristiq, Edronax, Lexapro, and Remeron
Antipsychotics Mellaril, Trilafon, and Orap Navane, Clozaril, Zyprexa, Geodon, and Seroquel
Cardiac Drugs Cardioquin and Ticlid Cardizem
Allergy medications Benadryl (diphenhydramine), Unisom (doxylamine), Dimetapp (Brompheniramine), Tagamet (cimetidine) Zyrtec (cetirizine), Claritin (Loratadine), Fexofenadine (Allegra), Ranitidine (Zantac)
Medications for Infectious Diseases Seldane and Cardioquin Crixivan, Invirase, Viracept, Rescriptor, Viramune, and Sustiva

The Bottom Line

If you are taking tamoxifen, talk to your doctor about any medications  that you are taking (including over-the-counter products, such as cold and allergy medications) to be sure that they don’t interfere with tamoxifen.

All articles are reviewed and approved by Dr. Diana Zuckerman and other senior staff.

Reference:

  1. Zosia Chustecka. Medscape News. Drugs to Avoid in Women Taking Tamoxifen. May 05, 2010. Accessed December 2017 Available online: https://www.medscape.com/viewarticle/721306

Question: I Have Been Diagnosed with Breast Cancer. What Are My Options so That I Can Still Have Breasts?


Q: I have been diagnosed with breast cancer. What are my options so that I can still have breasts?

A. We’re not doctors and we don’t provide medical advice, but I can tell you what we know based on research and from speaking with many experts and with women who have had breast implants. If you have been diagnosed with early stage breast cancer (stage I, IIa, IIb, or IIIa) , you probably can keep your breasts, and have a lumpectomy rather than a mastectomy (which removes the entire breast). Early-stage breast cancer patients who undergo a lumpectomy (which removes only the cancer and a small area around it) that is followed by radiation will live just as long as women who have a mastectomy instead.  In fact, the latest research indicates that women with early-stage breast cancer who have a lumpectomy live significantly longer than women of the same age and diagnosis who undergo mastectomy.

Experts recommend a lumpectomy with radiation for most women because it is less traumatic physically and emotionally, and avoids the problems from reconstructing a breast. For more information about this, see a booklet printed by the National Cancer Institute, the NIH, AHRQ, and the National Research Center for Women & Families here.

If you have been diagnosed with a pre-cancerous condition such as Stage 0 breast cancer, including ductal carcinoma in situ (DCIS) or lobular carcinoma in situ (LCIS), it is very unlikely that you need a mastectomy. Women with LCIS do not have breast cancer and most will never get breast cancer. They do not need a mastectomy or even a lumpectomy, although they do need regular mammograms. Most women with DCIS can choose lumpectomy with radiation, rather than mastectomy. For more information, see our booklet here.

For women with breast cancer who want to have breasts, the preferred choice is usually to keep their breasts (rather than remove their breasts and create new ones). Although a lumpectomy can make the breast smaller or change the shape, it will still have the sensation of a natural breast. In contrast, a woman who has a mastectomy with reconstruction, either with implants or with tissue transferred from elsewhere in her body, will have “breast shapes” that do not have any feeling. They are numb. Reconstruction also requires at least two surgeries. Reconstructed breasts may look fuller or “younger” but when the options are explained to them, many women would prefer to have sensation in their breast (or breasts), and would prefer not to have to worry about complications and the need for additional surgery.

If a woman needs to have a mastectomy, because the DCIS has spread throughout the breast or the cancer is large, there are several choices for reconstruction: saline breast implants, silicone breast implants, and moving tissue to create a new breast, such as a TRAM flap (Transverse Rectus Abdominis Myocutaneous flap) or DIEP flap (Deep Inferior Epigastric Perforator flap).

Many plastic surgeons know how to reconstruct breasts using breast implants, but few are skilled at moving tissue (which is called autologous tissue transfer). That is one of the reasons why so many plastic surgeons recommend breast implants.

Saline or Silicone? Some surgeons prefer silicone gel breast implants to saline, because they feel more natural. However, saline breast implants are approved by the FDA as “reasonably safe” and silicone gel implants are not. That is why women getting silicone gel breast implants must agree to be in a study. The goal is to find out how many complications or problems arise in these women in order to decide whether they are safe enough to approve. You would be part of an experiment to find out if the implants are “safe enough” for other women.

One problem with silicone breast implants is that they can break without a patient knowing it. Although less embarrassing than an instant deflation (which is likely with saline), breakage without symptoms is a bad thing, not a good thing. If silicone gel breast implants break and leak, the silicone can get into lymph nodes and travel to the lungs, liver, and brain. No research has been done on those risks, but a study by scientists at the National Cancer Institute found that women with breast implants were twice as likely to die from brain cancer or lung cancer compared to other plastic surgery patients. More research is needed, but those findings are cause for concern.

If saline implants break they are usually easy to remove. If silicone implants break, they can leak and can be extremely difficult and expensive to remove carefully. For that reason, we believe that saline are safer than silicone, even though both have very high complication rates.

Risks. All breast implants, even saline implants, are enveloped in an outer shell made of silicone. The envelope also contains other chemicals and heavy metals, such as microscopic amounts of platinum or tin, which vary during the manufacturing process. Unfortunately, some women have a reaction to those substances. Although silicone is considered “biocompatible” and most people don’t have an immediate allergic or autoimmune response, some people do, and many more develop a response years later.

It’s impossible to predict who will have problems with breast implants, and who won’t. It’s important to know that all implants will eventually break, sometimes within a few months or years, and usually within 10 years. Sometimes women who have a mastectomy get breast implants to replace one breast and to make the other breast look more similar to the replaced breast. However, it’s important to know that either silicone or saline breast implants interfere with mammograms. They show up white on the film, hiding tumors that are above or below.

Alternatives to Implants. An alternative to breast implants is “autologous tissue transfer,” such as the TRAM flap and DIEP flap procedures. These procedures use a woman’s own fat and tissue is used to reconstruct the breast. Many women prefer it to implants because it feels more natural and apparently lasts for a very long time (possibly forever, although the procedure has mostly been done in the last 15 years so it’s impossible to say). However, both the TRAM flap and DIEP flap procedures are more expensive than implants, require an especially skilled surgeon for a good result, and the healing process usually takes at least several months and can be painful. Women are only able to get this surgery if they have enough body fat in their abdomen area or back to form breasts. And, like a breast implant reconstruction, the breast has no feeling. For a woman who has the tissue transferred from her abdomen area (in an operation that has been compared to a “tummy tuck”), there is some loss of muscle in that area. That can be a problem for athletic women, but many other women don’t mind.

The DIEP flap is a similar type of reconstruction but does not remove any muscle. Instead, for the DIEP flap, the surgeon only removes fat and other tissue and makes a small cut in the abdominal muscle. Since no part of the abdominal muscle is removed, patients are able to maintain abdominal strength, making this surgery a better option for most women, especially those who are physically active.

Fortunately, TRAM flaps and DIEP flaps are covered by some health insurance companies. These are complicated surgeries with long recovery times and you would need to find a physician who is very experienced doing these procedures, and we highly recommend asking the doctor to put you in touch with other patients who were happy with the reconstruction.

 

For examples of women who had less pain and other symptoms after their implants were removed, see the personal stories on our website at http://www.breastimplantinfo.org/personal-stories/. You also might want to check out www.explantation.com to hear from women who have had their implants removed and not replaced. Many felt healthier, happier, and more attractive afterwards.

We hope this information is helpful. For more information, check out http://www.breastimplantinfo.org/breast-reconstruction/surgical-alternatives/ or feel free to write to us at info@center4research.org / info@stopcancerfund.org

The comments and statements of the National Research Center for Women & Families are believed and intended to be accurate, and where applicable, based on scientific literature. NRC’s statements do not constitute medical diagnoses, medical advice, plans of treatment, or legal opinion, and we are not responsible for the use or application of this information. All medical information should be reviewed with your health care practitioner.

We hope that the information we’ve provided is helpful. In order to maintain this free service to all women and their families, we invite your tax-deductible contributions to NRC (see http://www.center4research.org/contribute/ )

Are Mastectomies Necessary for Women with BRCA1 or BRCA2? What About for Women Without the Breast Cancer Gene?

Diana Zuckerman, PhD, and Megan Polanin, PhD, Cancer Prevention & Treatment Fund

When Angelina Jolie publicly announced her double mastectomy in 2013, she was praised for possibly saving many women’s lives. But we know more today than we did then and experts now agree that too many women are undergoing unnecessary mastectomies. Here are the facts.

A review of 10 studies found that the risk of getting breast cancer for an average woman with BRCA1 is 57%. The risk is 49% for a woman with BRCA2.[1] Keep in mind that for younger women, the lifetime risk of breast cancer is very different from the risk of getting breast cancer in the next 10 years or even 20 years. According to experts, a 40-year-old woman with the BRCA1 gene has a 14% chance of getting breast cancer before she turns 50.[2] That is not nearly as frightening, and with regular screening and all the progress in breast cancer treatments, the survival rate from breast cancer is higher than ever. Many breast cancer patients live long and healthy lives.

Most women are diagnosed with breast cancer at early stages, making it safe to undergo a lumpectomy (which removes just the cancer) rather than a mastectomy (which removes the entire breast). Yet American women are undergoing prophylactic mastectomies at a higher rate than women in other countries — many of them medically unnecessary.[3] Breast cancer experts believe that many women undergoing mastectomies do not need them and are getting them out of fear, not because of the actual risks.

In recent years, we have seen an increase in women with early-stage breast cancer choosing to get a double mastectomy. For example, a 2015 study conducted by researchers at Vanderbilt University reported that, for women diagnosed with early-stage breast cancer in one breast, the rates of double mastectomy increased from 2% to 11% from 1998 to 2011.[4] Researchers found that decisions to have a double mastectomy increased more for two groups of women: 1) Women with ductal carcinoma in situ (DCIS) where there are abnormal cells inside a milk duct in the breast that won’t spread and aren’t dangerous and 2) Women with cancer only in the breast that has not spread to the lymph nodes.

This year, researchers from Emory University and colleagues published a study focused on women diagnosed with early-state breast cancer in one breast.[5] They found that, from 2004 to 2012, the percentage of these women 45 years or older who got double mastectomies more than doubled from 4% to 10%. For women ages 20-44, the percentage tripled from 11% to 33%. Researchers found that it mattered where women lived in the United States. For example, in five Midwestern states (Nebraska, Missouri, Colorado, Iowa, and South Dakota), 42% of the women who got surgery decided to get a double mastectomy.

For many years, experts have known that women who undergo lumpectomies for a non-invasive condition called ductal carcinoma in situ (DCIS) or for early-stage breast cancer live just as long as women undergoing mastectomies. However, the latest research goes a step further: a study conducted in the Netherlands of more than 37,000 women with early-stage breast cancer found that the women undergoing lumpectomies were more likely to be alive 10 years later than women with the same diagnosis who underwent a single or double mastectomy.[7] They were also less likely to have died of breast cancer.

In 2016, Harvard cancer surgeon Dr. Mehra Golshan published a study of almost half a million women with breast cancer in one breast. She reported that those undergoing double mastectomies did not live longer than women undergoing a mastectomy in only one breast.[6]

These are just the most recent studies. For more information about the many studies that show the benefits of less radical surgery, see this article.

The bottom line is that women with DCIS or early-stage breast cancer have more effective and less radical treatment options than mastectomy. We need to stop thinking of mastectomy as the “brave” choice and understand that the risks and benefits of mastectomy are different for every woman with cancer or the risk of cancer. In breast cancer, any reasonable treatment choice is the brave choice.

The research clearly shows that mastectomies are not the best choice for most women if they want to live longer. Women should be aware of treatment choices for breast cancer and encouraged to make decisions based on their own unique situations. For each woman, it is important to weigh her own risk of cancer — in the next few years, and not just over her lifetime – and the risks of various treatments. Each woman should make the decision that is best for her, based on the facts, not on fear.

All articles are reviewed and approved by Dr. Diana Zuckerman and other senior staff. 

References

  1. Chen, S., & Parmigiani, G. (2007). Meta-analysis of BRCA1 and BRCA2 penetrance. Journal of Clinical Oncology, 25(11), 1329-1333.
  2. Chen, S., Iversen, E. S., Friebel, T., Finkelstein, D., Weber, B. L., Eisen, A., … & Corio, C. (2006). Characterization of BRCA1 and BRCA2 mutations in a large United States sample. Journal of Clinical Oncology, 24(6), 863-871.
  3. Metcalfe, K. A., Birenbaum‐Carmeli, D., Lubinski, J., Gronwald, J., Lynch, H., Moller, P., … & Kim‐Sing, C. (2008). International variation in rates of uptake of preventive options in BRCA1 and BRCA2 mutation carriers. International journal of cancer, 122(9), 2017-2022.
  4. Kummerow, K. L., Du, L., Penson, D. F., Shyr, Y., & Hooks, M. A. (2015). Nationwide trends in mastectomy for early-stage breast cancer. JAMA surgery, 150(1), 9-16.
  5. Nash, R., Goodman, M., Lin, C. C., Freedman, R. A., Dominici, L. S., Ward, K., & Jemal, A. (2017). State variation in the receipt of a contralateral prophylactic mastectomy among women who received a diagnosis of invasive unilateral early-stage breast cancer in the United States, 2004-2012. JAMA surgery.
  6. Wong, S. M., Freedman, R. A., Sagara, Y., Aydogan, F., Barry, W. T., & Golshan, M. (2017). Growing use of contralateral prophylactic mastectomy despite no improvement in long-term survival for invasive breast cancer. Annals of surgery, 265(3), 581-589.
  7. van Maaren, M. C., de Munck, L., de Bock, G. H., Jobsen, J. J., van Dalen, T., Linn, S. C., … & Siesling, S. (2016). 10 year survival after breast-conserving surgery plus radiotherapy compared with mastectomy in early breast cancer in the Netherlands: a population-based study. The Lancet Oncology, 17(8), 1158-1170.
  8. Hwang, E. S., Lichtensztajn, D. Y., Gomez, S. L., Fowble, B., & Clarke, C. A. (2013). Survival after lumpectomy and mastectomy for early stage invasive breast cancer. Cancer, 119(7), 1402-1411.
  9. Kurian, A. W., Lichtensztajn, D. Y., Keegan, T. H., Nelson, D. O., Clarke, C. A., & Gomez, S. L. (2014). Use of and mortality after bilateral mastectomy compared with other surgical treatments for breast cancer in California, 1998-2011. JAMA, 312(9), 902-914.

Are breast implants safe? What is FDA’s Track Record?

Diana Zuckerman, PhD, Cancer Prevention & Treatment Fund

In 2013, a study showed that a rare cancer of the immune system, ALCL, which had previously been linked to saline breast implants and silicone breast implants, was caused by breast implants and could be fatal.  The latest research indicates that this cancer is sometimes cured by removing the breast implants, but at other times also requires radiation and chemotherapy; in some cases, the patients died despite treatment. Although the FDA had reported in 2011 that ALCL might be caused by breast implants, the agency didn’t update its website when the 2013 study was published.  It took the FDA more than 3 more years to revise articles on its website indicating that breast implants caused ALCL ( to conclude that breast implants could cause ALCL. The FDA reported that they have received 359 reports of ALCL among women with breast implants through February 2017. It’s likely there are still numerous unreported cases; for example, Australia’s medical agency estimates that one in 1,000women with breast implants develops ALCL.  There is no reason to think American women would be less likely to develop ALCL, and that would result in several thousand U.S. women developing ALCL

This is just the latest bad news for women with breast implants, and for the government agencies that have allowed them on the market with inadequate studies or warnings.  For example, in 2011, tens of thousands of defective breast implants made by PIP were recalled in Europe. An article in the December 2012 issue of the British medical journal Reproductive Health Matters explains how these developments illustrate the strengths and weaknesses of the safeguards intended to protect patients in different countries from unsafe breast implants and other medical devices.  In the U.S., breast implants are regulated as high-risk medical devices that must be proven reasonably safe and effective in clinical trials and subject to government inspection before they can be sold. This standard is higher than the FDA requires for hip joints, numerous cardiac devices, and many other medical implants. In contrast, clinical trials and inspections have not been required for breast implants or other implanted devices in Europe. As a result of these differing standards, the PIP breast implants that were recalled across Europe had already been removed from the U.S. market years earlier. The FDA was justifiably proud that they had done a better job of protecting breast cancer patients and cosmetic augmentation patients than the EU regulatory system. Nevertheless, the FDA track record on breast implants shows how limited those safeguards can be. The FDA required two breast implant companies to conduct enormous 10-year studies of breast implants, but has done little to ensure that the studies are providing useful information to patients.

The authors conclude that neither the European Union nor the U.S. has used their regulatory authority to ensure the long-term safety of breast implants. However, in 2012 the EU announced regulatory changes that could improve that situation. In addition, the CEO of PIP was sentenced to 4 years in prison by a French Court, and in January 2017, a French court demanded that the German regulatory company that had certified PIP implants as safe pay $60 million euros to women harmed by PIP implants. This is only 3,000 euros each to 20,000 women, however.

Meanwhile, the FDA shows no indication that they will improve their safeguards on breast implants or other medical implants; in fact, those safeguards have weakened since 2012.

For more information about ALCL caused by breast implants, see:

Miranda RN, Aladily TN, Prince HM, et al: Breast implant–associated anaplastic large-cell lymphoma: Long-term follow-up of 60 patients. J Clin Oncol 32:114-120, 2014.

Mazzucco, AE.  Next Steps for Breast Implant-Associated Anaplastic Large-Cell Lymphoma. J Clin Oncol, 2014.  Early Release publication. June 16, 2014.