Hormonal Therapy for Ductal Carcinoma In Situ (DCIS)

Diana Zuckerman, PhD and Danielle Shapiro, MD, MPH, 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, at which point it is called invasive. 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, but 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]

Some women also try hormone therapy such as tamoxifen or aromatase inhibitors. That is the focus of this article.

DCIS does not need to be treated immediately. A woman can spend a few weeks after her diagnosis to talk with her doctors, learn the facts about her treatment choices, and think about what is important to her before she chooses which kind of treatment to have.

Hormonal Therapy

Hormonal therapy is recommended for some women with DCIS to help prevent breast cancer from developing and to prevent DCIS from returning after it has been surgically removed.  It is only effective for women whose DCIS is “estrogen receptor positive”, which DCIS usually is.

Hormonal therapy is taken as a pill every day for at least 5 years. Side effects include increased risk of endometrial cancer, severe circulatory problems, or stroke. In addition, hot flashes, vaginal dryness, abnormal vaginal bleeding, and a possibility of premature menopause are common for women who were not yet menopausal when they started treatment.[1]

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 (8.2% in women taking tamoxifen vs. 13.4% in 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 (from 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]

What is the benefit of hormone therapy for lumpectomy patients who do not undergo radiation therapy?

Although radiation therapy is usually recommended for lumpectomy patients, it is inconvenient and many women prefer to avoid it.  In addition, radiation is only beneficial for preventing cancer in the one breast, while hormone therapy helps prevent cancer in both breasts. A study of more than 1,700 women with DCIS who underwent a lumpectomy evaluated radiation and/or tamoxifen.  The women were randomly assigned either to radiation, tamoxifen, radiation plus tamoxifen, or no treatment after surgery. 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%. Interestingly, 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]

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]

Side Effects

While there are benefits to using hormonal therapy, tamoxifen and aromatase inhibitors carry risks of serious harms. Because estrogen plays an important role in maintaining strong bones and healthy cholesterol, blocking estrogen can put healthy women at greater risk for heart disease and osteoporosis.

Tamoxifen:

  • endometrial (uterine) cancer- for every 1,000 women, 2 more will develop uterine cancer
  • blood clots- for every 1,000 women, 3 more will develop potentially dangerous blood clots
  • strokes-  for every 100 women, 1 will develop a stroke
  • cataracts
  • hot flashes
  • vaginal discharge
  • vaginal bleeding

source: Medscape

Aromatase Inhibitors:

  • uterine cancer-  for every 1000 women, 20 more will develop uterine cancer
  • blood clots- for every 1,000 women, 20 more will develop a blood clot
  • strokes- for every 100 women, 2 more will develop a stroke
  • Joint pain for every 1000 women, 20 to 100 more will develop joint pains
  • hot flashes
  • vaginal bleeding
  • vaginal discharge

source: Medscape

The Bottom Line

In women diagnosed with DCIS, hormonal therapy can help prevent DCIS from recurring.  If a woman doesn’t undergo radiation therapy, hormonal therapy can reduce her chances of  invasive cancer in the opposite breast, but not invasive cancer in the same breast. And, hormonal therapy used in addition to radiation treatment apparently has no benefit, but does have added risks.

Perhaps most important, women who take hormonal therapies do not live any longer than women who don’t.

Too often, women with DCIS are encouraged to undergo radiation as well as hormonal therapy, but as you can see, the benefits of doing both are not greater than the benefits of choosing one or the other. And, the benefits of either radiation or hormonal therapy are primarily for reducing the chances of recurrence, but there is no benefit in terms of living longer.  Fortunately, almost all women with DCIS will live regardless of which of these treatments they have.

Talk to your doctor about which treatment options may be right for you.

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

Footnotes:

  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
  5. Medscape. Drugs & Diseases. Available online: https://reference.medscape.com/drug/soltamox-tamoxifen-342183#4 and https://reference.medscape.com/drug/arimidex-anastrozole-342208#4