2015 Breast Cancer Symposium Clinical Conversations: Breast Cancer Risk and Risk Reduction (General Session 4)

Dec 11, 2015

The Breast Cancer Symposium eQ&A series discusses some of the unanswered questions posed by attendees of the 2015 Breast Cancer Symposium during panel discussions.

Banu Arun, MD, of The University of Texas MD Anderson Cancer Center, helped lead a General Session discussion during the 2015 Symposium on “Breast Cancer Risk and Risk Reduction.” Other speakers included:

  • Frank A. Vicini, MD, 21st Century Oncology/Michigan Healthcare Professionals
  • Kelly Hunt, MD, The University of Texas MD Anderson Cancer Center
  • Sarah M. Friedewald, MD, Feinberg School of Medicine, Northwestern University
  • Jeffrey N. Weitzel, MD, City of Hope
  • Benjamin D. Smith, MD, The University of Texas MD Anderson Cancer Center
  • Eun-Sil Shelley Hwang, MD, MPH, Duke University

In the following article, Dr. Arun addresses some of the questions that did not get asked during the panel discussion. The session also included a debate on high-risk pathology by Dr. Smith and Dr. Hwang, which can be viewed exclusively on ASCOconnection.org.

Which population of patients with ductal carcinoma in situ (DCIS) would you give hormone therapy to? Would you give hormone therapy to all patients?

BA: Studies have indicated that patients who are estrogen receptor (ER)-positive with DCIS receive the most benefit. Therefore, in my practice we would offer hormone therapy to ER-positive patients with DCIS. In most populations, patients who are ER-positive receive the most benefit from hormone therapy because of the mechanism of action. Tamoxifen reduces the risk of invasive ER-positive breast cancer. We know that patients with ER-positive DCIS might have a higher risk of developing contralateral or new DCIS that are ER-positive as well, so those patients will most benefit from tamoxifen.

What about the Oncotype DCIS test? Can that study predict which patients should receive hormone therapy for breast cancer?

BA: This question would perhaps be better answered by my radiation oncology colleagues. The Oncotype DCIS study, as outlined in the May 2013 issue of Journal of the National Cancer Institute, was not designed to answer the question of which patients would benefit from tamoxifen in regard to the Oncotype score. The Oncotype DX breast cancer assay was performed for patients with DCIS treated with surgical excision without radiation in the Eastern Cooperative Oncology Group E5194 study. The results of the study did not provide any data on possible hormone therapy treatment options. Therefore, we cannot use Oncotype for tamoxifen decision making because we have no data.

For more information about the Oncotype DCIS study, check out the paper by Solin LJ et al., titled “A multigene expression assay to predict local recurrence risk for ductal carcinoma in situ of the breast.”

What is the benefit of chemotherapy prevention in patients with DCIS who are ER-negative?

BA: This question is very similar to the first one, which asked which population of patients with DCIS you would give hormone therapy to. The answer, based on reported studies, was that patients who were ER-positive with DCIS received the most benefit. Those same studies have shown that hormone therapy most probably will not work on ER-negative patients. Therefore there is little benefit in chemotherapy prevention in patients with DCIS who are ER-negative.

In clinical practice, what would you recommend for a patient who has a PALB2 mutation and wants a mastectomy for contralateral breast cancer prevention?

BA: This is a very good question. Right now, there is absolutely no prospective data about contralateral breast cancer rates in women with PALB2 mutations and a diagnosis of breast cancer. Whether a patient chooses a mastectomy is their personal choice.

In patients with PABP2 mutations, we know that the risk of breast cancer can range anywhere from 20% to 40% in unaffected women. In affected women, we do not know the rate of contralateral breast cancer, therefore we cannot quote it. But we know that women with breast cancer, regardless of whether they have a PABP2 mutation or not, have a risk of contralateral breast cancer of approximately 0.5% per year (with some studies indicating a risk of up to 1% per year).

Regardless of PABP2 mutations, women with breast cancer are at an increased risk for contralateral breast cancer. Whether those patients want a preventative surgery is a personal choice. At this time, we neither know whether a PALB2 mutation increases that risk for contralateral breast cancer nor do we know if that mutation increases the benefit from mastectomy.

Can you state with certainty whether tamoxifen will reduce risk in BRCA1?

BA: We cannot state with certainty that tamoxifen will reduce risk in BRCA1. During the panel discussion, I indicated that there are no prospective studies with tamoxifen in BRCA1-positive high-risk women. But knowing that tamoxifen reduces the risk of ER-positive breast cancer and that BRCA1 mutation carriers have a 70% chance of developing ER-negative breast cancer, tamoxifen most probably will not be preventive in these women; however, as discussed, there is no prospective data. Some BRCA2-positive high-risk women might benefit from tamoxifen.

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