Omit Chemotherapy for Luminal A Breast Cancer?

May 2016, Vol 7, No 4

Younger patients with luminal A subtype breast cancer may not need chemotherapy, according to a Danish trial presented by lead investigator Torsten O. Nielsen, MD, PhD, Professor, University of British Columbia, Vancouver, Canada, at the 2015 San Antonio Breast Cancer Symposium. Patients with luminal A biological subtype breast cancer have an excellent prognosis, even 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,” stated Dr Nielsen.

He emphasized that randomized controlled trials are needed to confirm the findings, which were based on an 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. It has been difficult to do randomized trials without offering women with breast cancer adjuvant chemotherapy, because we know it helps them. Larger prospective studies are needed to change practice,” explained Dr Nielsen.

No Chemotherapy Benefit in Luminal A Breast Cancer

The study was based on tissue samples from the Danish Breast Cancer Cooperative Group 77B trial of 1146 premenopausal women with node-positive, high-risk breast cancer and any hormone receptor or HER2 status. The high-risk features included tumors of ≥5 cm 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 and radiation. The patients were randomized to 2 no-chemotherapy groups that received levamisole or no agent (control), or to 2 chemotherapy arms that received cyclophosphamide alone or cyclophosphamide, methotrexate, and 5-fluorouracil. Cyclophosphamide as well as the triplet of cyclophosphamide, methotrexate, and 5-fluorouracil improved the 10-year and 25-year invasive disease-free survival (DFS).

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

Luminal A subtype breast cancer was defined as being estrogen or progesterone receptor–positive and having HER2-negative status. Of 633 immunohistochemistry analyzed samples, 165 were identified as subtype luminal A.

Patients with luminal A subtype breast cancer had similar 10-year DFS with and without chemotherapy, regardless of their nodal status and use of hormonal therapy. Patients with nonluminal A subtype breast cancer were 50% more likely to survive disease-free at 10 years if they received chemo­therapy. The interaction between chemotherapy and luminal A and non­luminal breast cancer subtypes was significant (<em>P</em> &lt;.05).

Dr Nielsen gave several caveats about this trial, including that patients received older chemotherapies, rather than 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,” said Virginia G. Kaklamani, MD, DSc, Leader, Breast Cancer Program, Cancer Therapy and Research Center, the University of Texas Health Science Center at San Antonio, who was not involved in this study. “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.”

Dr Kaklamani said that 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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