09 June 2016

A study presented at the recent American Society of Clinical Oncology meeting evaluated the use of extended endocrine therapy in post-menopausal women. I’ve covered some of the basics of endocrine therapy for breast cancer in a previous post. In 2012, results of the ATLAS Trial were published, and found that when tamoxifen was given for 10 years instead of the standard 5, improvements were noted in overall and disease free survival.

Up until this point, no study has demonstrated similar findings for post-menopausal women taking aromatase inhibitors. Results of the MA.17R study were reported at the 2016 ASCO meeting, Patients in the study had already completed at least 5 years of endocrine therapy with the aromatase inhibitor letrozole. They were then randomized to receive either an additional 5 years of letrozole or a placebo. Median follow up was 6.3 years.

The key study findings were as follows:
  Disease free survival was 95% in the treatment group and 91% in the placebo group, a 34% reduction. This was statistically significant.
–  Contralateral breast cancer (a new cancer developing in the opposite breast) occurred in 1.4% of the treatment group, and 3.2% of the placebo group a 58% reduction. This was also statistically significant.
–  Overall survival was the same in both groups.
–  More bone fractures (14% vs. 9%) and new-onset osteoporosis (11% vs. 6%) were seen in the patients undergoing extended endocrine therapy – it is well known that these medications accelerate bone loss. These findings were statistically significant.
– Rate of discontinuing therapy was 5.4% in the letrozole group, and 3.7% in the placebo group.

Several points were brought up in the discussion immediately following the presentation as well as in post-plenary “town hall” style session held later in the day, including:

–  It is not clear what the long-term effects of medications used to treat bone loss will be – if patients are on endocrine therapy for longer periods of time, they likely will need to be on the bone protective medications for longer as well.
–  Reported quality of life was similar in both groups, as reported by Dr. Julie Lemieux. However, as Dr. Don Dizon noted: “without compromising quality of life” isn’t the same as “everything’s peachy.”

– It was noted that the patients enrolled in the study were self-selected which may bias the results. As they had already completed at least 5 years of letrozole therapy, these patients likely had few existing side effects from treatment. Concern was raised in the post-plenary discussion that we may see more of an impact on quality of life if a broader population of women is treated with extended endocrine therapy.
Dr. Lisa Carey noted that adherence to endocrine therapy remains a significant issue in part due to medication side effects. While the rate of discontinuation of therapy in this study was low, this does not reflect real-world experience.

The disease free survival improvement and contralateral breast cancer reduction were widely reported in the press as percentages (34% disease free survival benefit, 58% reduction in contralateral breast cancer). It is important to realize that the absolute benefits are very small – only a few percentage points. While the results achieved statistical significance, they may or may not be significant to an individual patient. It is important that patients understand the concept of absolute risk vs. relative risk.

Professor Ian Smith, who discussed the abstract during the plenary session, concluded by saying that the MA.17R findings do not justify extended endocrine therapy in all patients. Rather, patients with more aggressive features such as larger tumors, positive lymph nodes, and higher cell grade may benefit. He called for physicians to carefully discuss the study results with their patients, and allow them to participate in the decision for or against extended endocrine therapy.

This conclusion prompted the following Twitter exchange with an oncology colleague:

While it should go without saying that we need to discuss study results as well as advantages and disadvantages of treatment with our patients, this point is not emphasized enough during national presentations. The lead author, Dr. Goss, commented during the post-plenary discussion that he is not specifically recommending extended hormonal therapy. Rather, he acknowledged that this is a decision that needs to be made by an individual patient, in consultation with her physician, after carefully reviewing all of the information. The study received a significant amount of media attention, and the discussion at the conference session was very spirited. At the end of the day, it’s important that patients to realize that we don’t have a definitive answer for the individual.

It is also important not to forget the impact of lifestyle factors in terms of reducing risk of recurrence. Regular exercise, weight maintenance, healthy food choices, and moderation in alcohol intake all will help reduce the risk not only of breast cancer recurrence, but also of cardiovascular disease, which remains the number one killer of women in the United States.

Additional Reading:
ASCO Post Overview of MA.17R
Changing Adjuvant Breast Cancer
Dr. Elaine Schattner in Forbes

 

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  1. […] In June, a study was presented which suggested that 10 years of endocrine therapy in post-menopausal women might be superior to 5 years of treatment, which had been the standard. The study noted that disease free survival was improved and development of new breast cancers were reduced in the extended therapy patients, but there were more side effects. A conclusion was that extended therapy might be appropriate for higher risk patients – those who based on certain tumor factors we suspect might have a higher risk of recurrence. A challenge has been that we do not have good tests to tell us with certainty which patients will truly benefit from a longer course of therapy. […]

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