Omit Chemotherapy for Premenopausal Luminal A Breast Cancer?

Torsten O. Nielsen, MD, PhD

San Antonio Breast Cancer Symposium

Younger patients with luminal A subtype breast cancer may not need chemotherapy, according to a Danish trial presented at the 2015 San Antonio Breast Cancer Symposium. Luminal A biological subtype breast cancer has an excellent prognosis, even in high-risk patients, the study suggests.

“A large body of evidence suggests that luminal type A breast cancer has the best prognosis of all breast cancer subtypes. It has been difficult to do randomized trials without offering women with breast cancer adjuvant chemotherapy, because we know it helps them,” stated lead investigator Torsten O. Nielsen, MD, PhD, University of British Columbia, Vancouver, Canada.

Nielsen emphasized that randomized controlled trials are needed to confirm the findings he reported, which were based on analysis of tissue samples from an older phase 3 trial initiated in 1977 to compare chemotherapy versus no chemotherapy.

“Nevertheless, this is one more piece of evidence of an evolving story suggesting that women with this low-risk type of cancer do not benefit from chemotherapy. Larger prospective studies are needed to change practice,” explained Nielsen.

The study was based on tissue samples from the DBCG 77B trial of 1146 premenopausal women with node-positive, high-risk breast cancer with any hormone receptor or HER2 status. High-risk features included tumors of 5 cm or greater or node-positive status; hormone receptor and HER2 status were not ascertained, because this was not standard of care when the trial was initiated in 1977.

All women received standard treatment for that time consisting of mastectomy plus axillary node dissection plus radiation. They were randomized to levamisole (control) versus cyclophosphamide or cyclophosphamide, methotrexate, and 5-fluorouracil (CMF). Both cyclophosphamide and CMF improved 10-year and 25-year disease-free survival (DFS).

For the present study using archival tissue analysis, the primary end point was 10-year DFS.

Luminal A subtype was defined as estrogen/progesterone receptor–positive and HER2-negative status. Of 633 samples analyzed by immunohistochemistry, 165 were identified as luminal A subtype.

Luminal A patients had similar 10-year DFS with and without chemotherapy regardless of nodal status and used hormonal therapy. Nonluminal A patients were 50% more likely to survive disease-free at 10 years if they were treated with chemotherapy. The interaction between chemotherapy and luminal A and nonluminal A subtypes was significant (P <.05).

Nielsen gave several caveats about this trial, including the fact that patients received older chemotherapies, not modern treatment with endocrine therapy, anthracyclines, or taxanes.

“We have prospective data on genomic profiling of tumors showing that these patients have a very good prognosis. We also have data on postmenopausal node-positive patients suggesting that chemotherapy does not benefit subtype luminal A breast cancer. These data in premenopausal women are exciting,” said Virginia Kaklamani, MD, leader of the Breast Cancer Program at the Cancer Therapy and Research Center and professor of medicine at The University of Texas Health Science Center at San Antonio, who was not involved in this study.

She said randomized controlled trials are needed to establish with certainty that premenopausal women with luminal A breast cancer can safely forego chemotherapy.

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