Verdict still out on loco-regional therapy for de novo metastatic breast cancer

By Joan Mancuso

Key points:

  • Whether to treat de novo metastatic breast cancer patients with a lumpectomy/ mastectomy and radiation has now become controversial, as in the past, a breast tumor was never removed.
  • Some clinical trial results have been inconclusive about the benefits of loco-regional therapy to a patient’s overall survival.
  • Oncologists await the results of the Eastern Cooperative Oncology Group 2108 clinical trial as a potential tie-breaker about the benefit of loco-regional therapy.

Whether to treat a primary breast tumor with loco-regional procedures to improve overall survival (OS) when a patient presents with de novo metastatic breast cancer (MBC) is controversial. De novo MBC occurs when the cancer has spread already to an organ or the bones at a patient’s first diagnosis of breast cancer. It occurs in roughly 6% of patients. The tendency has been not to remove the breast tumor with a lumpectomy or mastectomy, or treat it with radiation, once the cancer has already spread to distant sites.

The controversy was discussed by Dr. Seema Kahn at the 2017 annual San Antonio Breast Cancer Symposium in December, where she looked at the evidence for or against treating de novo MBC. The session was titled, Challenges in Advanced/Metastatic Breast Caner. Dr Kahn is professor of surgery at the Lynn Sage Breast Center, Northwestern University.

Awaiting the results of a tie-breaker

Two randomized prospective studies showed different approaches and produced different results in determining whether loco-regional intervention resulted in a survival advantage.

In the Tata Memorial Hospital study of 350 women in India, patients who underwent a mastectomy and removal of axillary lymph nodes as well as radiation did not have a better OS than women who received only chemotherapy. At 72 months, OS was 20.5% for those treated loco-regionally and 19.2% for those who did not have a surgical intervention.

Other results from the Turkish Federation of Breast Diseases Societies study presented in 2016 showed that patients who were randomized to receive either initial systemic therapy followed by loco-regional therapy for local progression, or initial loco-regional therapy followed by systemic therapy showed an advantage for patients who received surgery first. The study resulted in an OS advantage of 42% at 60 months for patients who received surgery first, compared to 24% for those who had initial systemic therapy.

However, the patients who had the greatest benefit were estrogen receptor-positive and HER2 negative, had solitary bone metastases and were younger than age 55. Whereas, patients with multiple live and/or lung metastases did not fare as well with initial surgery.

Given the conflicting results of the Tata Memorial Hospital and Turkish Federation studies, many oncologists are awaiting the results of the Eastern Cooperative Oncology Group (ECOG) 2108 prospective clinical trial, where all patients receive systemic therapy and those who show response/stable disease are then randomized to early loco-regional therapy, or to delayed loco-regional therapy if there is local progression. This clinical trial is no longer recruiting, and investigators have enrolled roughly 400 patients.