Category Archives: Breast Cancer

Summary of Published Study by MD Anderson Physicians on the Increase in Rare Diseases Among Women with Breast Implants

National Center for Health Research: September 17, 2018.


A study published in September 2018 in the medical journal Annals of Surgery, entitled US FDA Breast Implant Postapproval Studies: Long-term Outcomes in 99,993 Patients, concluded that “silicone implants are associated with an increased risk of certain rare harms” and that further study is needed “to inform patient and surgeon decision-making.”  The study is important because it is largest study to date, but it has limitations because it is based on data from flawed studies conducted by two implant companies, Mentor and Allergan.

The data collected from the two studies were supposed to be very similar, but because of how poorly the studies were conducted, they are not comparable.  Mentor’s data are focused on patients’ self-reporting on questionnaires, primarily on data of only 20% of the patients collected 7 years after the study was started. Allergan’s data are based on physicians’ diagnoses during the first two years after the patients had implant surgery.  Since patients’ self-reports at 7 years would be expected to include more complications than physicians’ diagnoses after 2 years, it is impossible to make meaningful comparisons between the two manufacturers. Nevertheless, it is important to note that the MD Anderson researchers found that the risks of certain autoimmune diseases increased by 800% (Sjogren syndrome), 700% (scleroderma), and 600% (arthritis) for the women with Mentor silicone gel breast implants compared to the general population of women of the same age and demographics.  Stillbirths increased by 450% in the women who became pregnant.  Other autoimmune and rare diseases were also significantly higher among women with Mentor silicone gel implants.  These diagnoses were also statistically significantly higher (although not as dramatically increased) for women with Allergan implants compared to the general population of women of similar demographics. Given the large percentage of women who were not in the study for more than 1 year, it is not possible to know how representative these findings are. However, these results certainly deserve careful attention.

It is also important to note that the women with saline breast implants who were in the Mentor and Allergan studies were not analyzed in the MD Anderson study.

FDA Response

In response to this important study, Dr. Binita Ashar of the FDA published an editorial in the same issue of the same medical journal, claiming that the MD Anderson study “failed to account for methodologic differences between studies, inconsistencies in the data, differential loss to follow-up, confound and other potential sources of bias.”  That is true.  However, Dr. Ashar did not mention that the FDA should take responsibility for all the shortcomings of the data that MD Anderson analyzed.  She did not mention that the flawed data were based on studies that were required by the FDA as a condition of approval for the breast implants made by Allergan and Mentor.  The data were flawed because women soon disappeared from the study, and the FDA did not require the companies to finish the studies, as they should have,

As a result of the FDA’s failure to enforce the study requirements, the large Allergan and Mentor studies used as the basis of the MD Anderson analyses were very flawed short-term studies rather than the 10-year studies that FDA had proudly said they were requiring.  Whereas the companies blamed the study shortcomings on the enormous number of women who “dropped out” of the study shortly after enrolling (including 80% of the women with Mentor implants after only 1 year), we have interviewed women who were enrolled in those studies who told us that they did not drop out of the studies – rather they were “dropped” from the study by the researchers without their consent.  They never heard from the researchers and hence had no opportunity to tell the researchers how sick they had become after getting breast implants.   Instead, several of those women went to the FDA this month to explain to FDA scientists what happened.  They told Dr. Ashar and other FDA officials that they were dropped from the studies.  They told Dr. Ashar and other FDA officials that they had suffered from autoimmune and connective tissue symptoms such as the ones reported in the MD Anderson study.  They told Dr. Ashar and the other FDA officials that despite being sick for years, they were unaware that breast implants could be the cause because neither the FDA nor their plastic surgeons had warned them of the risks.  When they finally found each other on social media (on Facebook pages joined by more than 50,000 women harmed by breast implants), they realized that removing their implants might help.  Much to their surprise, they experienced almost miraculous recoveries after their implants were removed by experienced explant surgeons.   The women told Dr. Ashar and other FDA officials that their symptoms disappeared entirely or improved by 85%.

The FDA editorial was written before Dr. Ashar met with the former implant patients this month, but she had previously met with several of the same women who had reported these same problems and recoveries after explant surgery.  So it is very discouraging that FDA staff have been and continue to be so close-minded about the risk of breast implants despite the MD Anderson analyses.

What Have we Learned from the MD Anderson Study?

We agree with the FDA and the MD Anderson researchers that these results can’t be considered conclusive, but the FDA needs to look at the data more carefully and require better studies so that they can reconsider their repeated claim that breast implants are only proven to cause local complications, such as leaking and painful implants.  Although the FDA admits that breast implants can cause a cancer of the immune system known as ALCL, they continue to quote industry-funded studies claiming that implants do not cause other systemic illnesses.  It should be obvious to open-minded scientists that if breast implants can cause cancer of the immune system, they can probably cause other serious immune system diseases and symptoms.  Moreover, the results of the MD Anderson study supports those concerns about autoimmune symptoms and diseases.

What should be the key information of importance to women considering breast implants or women who have them in their bodies? Clearly, these studies indicate that patients should report any new symptoms that develop after getting their implants, whether involving their breasts or other parts of their body.  Breast implant patients should know that the FDA recommends MRI imaging of silicone breast implants 3 years after the augmentation or reconstructive surgery and every 2 years thereafter.

  

Statement of Dr. Diana Zuckerman, President of the National Center for Health Research Regarding the New Study of 100,000 Women with Breast Implants

Dr. Diana Zuckerman, President of the NCHR: September 17, 2018.


In the largest study ever conducted of long-term health risks for patients with breast implants, researchers at The University of Texas MD Anderson Cancer Center have reported that women with silicone implants are more likely to be diagnosed with several rare diseases, autoimmune disorders, and other conditions.  These results are consistent with numerous previously published studies, but contradict the conclusions of studies funded by implant manufacturers or plastic surgery medical societies.

The study, published in the medical journal Annals of Surgery, is by researchers in MD Anderson’s Department of Plastic Surgery and is based on analyses of almost 100,000 patients with either saline or silicone implants. The information was derived from the FDA’s database dating back to 2005.  When the FDA approved silicone gel breast implants made by two manufacturers in 2006, the agency required that each of the manufacturers study at least 40,000 women for 10 years.  Those studies were started but never completed, making it impossible to determine the long-term risks of breast implants.  In the absence of such crucial studies, patients report that they were not warned about the risks when they decided to get breast implants.

We thank Mark W. Clemens, M.D., associate professor, Plastic Surgery, the senior investigator of this very important study.  The findings are consistent with what thousands of women with breast implants have reported in Facebook groups and other social media, and directly challenge the FDA’s claims that breast implants do not cause such diseases.  We urge the FDA to be more patient-centered and finally require independent studies be conducted of women before and after their breast implants are removed.  Many women have reported that their debilitating autoimmune symptoms decreased or disappeared after their breast implants were removed, but scientific data is needed to establish the rate of recovery.

Radiation Therapy for Ductal Carcinoma In Situ (DCIS)

Diana Zuckerman, PhD, Cancer Prevention and Treatment Fund.


In recent years, ductal carcinoma in situ (DCIS) has become one of the most commonly diagnosed breast conditions. It is often referred to as “stage zero breast cancer” or a “pre-cancer.” It is a non-invasive breast condition that is usually diagnosed on a mammogram when it is so small that it has not formed a lump. In DCIS, some of the cells lining the ducts (the parts of the breast that secrete milk) have developed abnormally, but the abnormality has not spread to other breast cells.

DCIS is not painful or dangerous, but it sometimes develops into breast cancer in the future if it is not treated. If it develops into breast cancer, it can spread.  If that happens, it is called invasive breast cancer. The goal of treating invasive cancer is to prevent it from spreading to the lungs, bones, brain, or other parts of the body, where it can be fatal. Since DCIS is not an invasive cancer, it is even less of a threat than Stage 1 or Stage 2 breast cancer, which are the earliest types of invasive cancer.[1]  For more information, see our free DCIS booklet, and our other articles on DCIS.

Most women with DCIS will never develop invasive cancer whether they are treated or not.  Unfortunately, it is impossible to predict which women with DCIS will develop cancer and which ones won’t. That’s why treatment is recommended. A woman with DCIS does not need all the same treatments as a woman diagnosed with invasive breast cancer, but surgery is almost always recommended. Most DCIS patients will choose a lumpectomy (which removes the DCIS but does not remove the entire breast), and radiation therapy is usually recommended for those women to destroy any stray abnormal cells in the same breast.[1]

Is Radiation Necessary?

Doctors usually recommend radiation therapy for lumpectomy patients, but since it is inconvenient and has some side effects, many women prefer to avoid it.  In fact, some DCIS patients decide to have a mastectomy because they do not want to undergo radiation.  However, mastectomy is a much more radical surgery and is very rarely a good idea for DCIS patients. That’s because almost all women with DCIS live long lives, and undergoing radiation does not affect whether DCIS patients live a long life or not.

Instead, the main advantage of radiation for DCIS is to prevent recurrence of DCIS in the breast where the DCIS was removed. A study of more than 1,700 women with DCIS who underwent a lumpectomy evaluated different treatment options.  The women were randomly assigned either to radiation, tamoxifen, radiation plus tamoxifen, or no treatment after surgery.  Undergoing radiation had a very small benefit for women in general, and has little impact on your chances of living a cancer-free life.

In women treated with radiation, about 10% developed DCIS or breast cancer within the next 10 years after surgery, and it made no difference whether these women took tamoxifen or not. And while the vast majority of women were alive 10 years later, their chances of survival were no different whether they were treated with radiation, tamoxifen, both, or neither.[4]  

For women who did not have radiation therapy, tamoxifen reduced the chances of developing DCIS within 10 years in the same breast by about 3% and the chances of developing DCIS in the other breast by about 1%. Tamoxifen did not significantly decrease the chances of developing invasive breast cancer in the same breast, and only reduced the chances of developing invasive cancer in the opposite breast by about 1%.[4]

So why do doctors so strongly recommend radiation and hormone therapy for DCIS?  Doctors tend to focus on reducing “relative risk” rather than actual risk. So, if a  treatment decreases the chances of recurrence by about 50% that sounds impressive — but 50% of a 16% chance is 8%, for example, and that isn’t much of a difference. And 50% of a 6% chance of recurrence is even less meaningful.  Most important, it doesn’t affect survival so women can skip radiation now and choose it later if they have a recurrence. In contrast, if a woman has radiation after a lumpectomy and later has a recurrence anyway, she can’t undergo radiation again.

When is radiation most important for DCIS?  It is more likely to benefit younger women (especially women diagnosed before age 40), women with more serious types of DCIS (a high grade DCIS called comedo), and women with a family history of breast cancer.

What is the benefit of hormone therapy for women also undergoing radiation therapy?

Tamoxifen blocks the effects of estrogen on breast cells, which can stop the growth of cancer cells that are sensitive to estrogen. A study of more than 1,800 pre-menopausal and post-menopausal women with DCIS evaluated the benefits of tamoxifen for women who had lumpectomy and radiation treatment. These women were randomly assigned to take tamoxifen for 5 years or a placebo (sugar pill). The study found that after 5 years, women who took tamoxifen were about 5% less likely to develop either DCIS or cancer in the same breast, cancer in the opposite breast, or distant cancer spread.  The difference was 8 of women taking tamoxifen compared to 13% of women taking placebo. However, the vast majority of women survived and they did not live any longer whether they took tamoxifen or not.[1]

For postmenopausal women, aromatase inhibitors may be used instead of tamoxifen. Aromatase inhibitors block the body’s ability to make estrogen. A study of more than 3,000 post-menopausal women with DCIS evaluated the benefits of hormone treatment for women who had lumpectomy and radiation treatment. These women were randomly assigned to take tamoxifen or anastrozole for 5 years. The study found that after 5 years, compared to women taking tamoxifen, the women taking anastrozole were 2% less likely to develop either DCIS or cancer in the same breast, cancer in the opposite breast, or distant cancer spread.  The difference was about 8% of women taking tamoxifen compared to 6% taking anastrozole.  As in the previous study, the vast majority of women survived and those taking anastrozole did not live any longer than women taking tamoxifen.[2]

That was a very small benefit for anastrozole compared to tamoxifen, and another study of post-menopausal women with DCIS found no difference between the two hormone treatments.[3].

Bottom Line:  Radiation and hormone therapy both have benefits for most women who undergo lumpectomy, because they decrease the chances of DCIS returning after surgery.  However, the benefits are quite modest and neither of these treatments affect how long women live, because almost all women diagnosed with DCIS are still alive 20 years later.

References:

  1. National Cancer Institute. Breast Cancer Treatment PDQ. (Feb. 2018). Available online: https://www.cancer.gov/types/breast/hp/breast-treatment-pdq#link/_1576_toc
  2. Margolese, Richard G et al. Anastrozole versus tamoxifen in postmenopausal women with ductal carcinoma in situ undergoing lumpectomy plus radiotherapy (NSABP B-35): a randomised, double-blind, phase 3 clinical trial.The Lancet. 2016;387(10021): 849 – 856.
  3. Forbes, John F et al. Anastrozole versus tamoxifen for the prevention of locoregional and contralateral breast cancer in postmenopausal women with locally excised ductal carcinoma in situ (IBIS-II DCIS): a double-blind, randomised controlled trial. The Lancet.2016;387(10021): 866 – 873.
  4. Cuzick, Jack et al. Effect of tamoxifen and radiotherapy in women with locally excised ductal carcinoma in situ: long-term results from the UK/ANZ DCIS trial. The Lancet Oncology. 2011; 12(1): 21 – 29

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