A 21-gene test performed on tumours could enable most patients with the most common type of early breast cancer to safely forgo chemotherapy, according to a landmark study.
Loyola Medicine oncologist Dr Kathy Albain, is among the main co-authors of the study and a member of the clinical trial’s steering committee. First author is Dr Joseph Sparano, of Montefiore Medical Centre in Bronx, New York. The study was published in conjunction with its presentation at the plenary session of the American Society of Clinical Oncology 2018 meeting in Chicago.
“With results of this ground-breaking study, we now can safely avoid chemotherapy in about 70% of patients who are diagnosed with the most common form of breast cancer,” Albain said. “For countless women and their doctors, the days of uncertainty are over.”
Albain, the Huizenga Family endowed chair in oncology research at Loyola University Chicago Stritch School of Medicine, has conducted research with the 21-gene test and also used it in her practice for years.
The test examines 21 genes from a patient’s breast cancer biopsy sample to determine how active they are. The tumour is assigned a “recurrence score” from 0 to 100; the higher the score, the greater the chance the cancer will recur in distant organs and decrease survival. If patients with higher scores receive chemotherapy, this risk of recurrence will be significantly reduced, enabling more patients to be cured.
Previously, the challenge doctors and patients have faced is what to do if a patient has a mid-range score. It was uncertain whether the benefit of chemotherapy was great enough to justify the added risks and toxicity. Previous studies demonstrated that patients with low scores (10 or lower) did not need chemotherapy, while women with high scores (above 25) did require and benefit from chemotherapy.
The new study examined the majority of women who fall in the intermediate range of 11 to 25.
The study enrolled 10,273 women who had the most common type of breast cancer (hormone-receptor positive, HER-2 negative) that had not spread to lymph nodes. Researchers examined outcomes of the 69% of patients who had intermediate scores on the 21-gene test.
Patients were randomly assigned to receive chemotherapy followed by hormonal therapy or hormone therapy alone. Researchers examined the chemotherapy and non-chemotherapy groups for several outcomes, including being cancer free, having cancer recur locally or to distant sites in the body and overall survival.
For the entire study population with gene test scores between 11 and 25-and especially among women aged 50 to 75-there was no significant difference between the chemotherapy and no chemotherapy groups. Among women younger than 50, outcomes were similar when gene test scores were 15 or lower. Among younger women with scores 16 to 25, outcomes were slightly better in the chemotherapy group.
“The study should have a huge impact on doctors and patients,” Albain said. “Its findings will greatly expand the number of patients who can forgo chemotherapy without compromising their outcomes. We are de-escalating toxic therapy.”
Background: The recurrence score based on the 21-gene breast cancer assay predicts chemotherapy benefit if it is high and a low risk of recurrence in the absence of chemotherapy if it is low; however, there is uncertainty about the benefit of chemotherapy for most patients, who have a midrange score.
Methods: We performed a prospective trial involving 10,273 women with hormone-receptor–positive, human epidermal growth factor receptor 2 (HER2)–negative, axillary node–negative breast cancer. Of the 9719 eligible patients with follow-up information, 6711 (69%) had a midrange recurrence score of 11 to 25 and were randomly assigned to receive either chemoendocrine therapy or endocrine therapy alone. The trial was designed to show noninferiority of endocrine therapy alone for invasive disease–free survival (defined as freedom from invasive disease recurrence, second primary cancer, or death).
Results: Endocrine therapy was noninferior to chemoendocrine therapy in the analysis of invasive disease–free survival (hazard ratio for invasive disease recurrence, second primary cancer, or death [endocrine vs. chemoendocrine therapy], 1.08; 95% confidence interval, 0.94 to 1.24; P=0.26). At 9 years, the two treatment groups had similar rates of invasive disease–free survival (83.3% in the endocrine-therapy group and 84.3% in the chemoendocrine-therapy group), freedom from disease recurrence at a distant site (94.5% and 95.0%) or at a distant or local–regional site (92.2% and 92.9%), and overall survival (93.9% and 93.8%). The chemotherapy benefit for invasive disease–free survival varied with the combination of recurrence score and age (P=0.004), with some benefit of chemotherapy found in women 50 years of age or younger with a recurrence score of 16 to 25.
Conclusions: Adjuvant endocrine therapy and chemoendocrine therapy had similar efficacy in women with hormone-receptor–positive, HER2-negative, axillary node–negative breast cancer who had a midrange 21-gene recurrence score, although some benefit of chemotherapy was found in some women 50 years of age or younger.
Joseph A Sparano, Robert J Gray, Della F Makower, Kathleen I Pritchard, Kathy S Albain, Daniel F Hayes, Charles E Geyer, Elizabeth C Dees, Matthew P Goetz, John A Olson, Tracy Lively, Sunil S Badve, Thomas J Saphner, Lynne I Wagner, Timothy J Whelan, Matthew J Ellis, Soonmyung Paik, William C Wood, Peter M Ravdin, Maccon M Keane, Henry L Gomez Moreno, Pavan S Reddy, Timothy F Goggins, Ingrid A Mayer, Adam M Brufsky, Deborah L Toppmeyer, Virginia G Kaklamani, Jeffrey L Berenberg, Jeffrey Abrams, George W Sledge