Triple-Negative BRCA Has Higher Mortality Risk

This report is part of a 12-month Clinical Context series.

By Michael Smith, North American Correspondent, MedPage Today

Published: May 03, 2012

Reviewed by Vandana G. Abramson, MD; Assistant Professor of Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee and Dorothy Caputo, MA, BSN, RN, Nurse Planner

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• Patients with stage I-III triple-negative breast cancer had a significantly higher risk of death (OR 8.3) in the first two years after diagnosis than women with ER+ or HER2+ disease.
• Patients with triple-negative disease were more likely to have metastases to the brain or lung, and less likely to have recurrence in the bones compared with ER+ or HER2+ patients.

Women with so-called triple-negative breast cancer had nearly three times the risk of death from the disease as women with the most common form of the disease, researchers reported.
And the risk was even higher in the first two years after diagnosis -- eight-fold compared with women with the most common form, they also had a markedly higher rate of death from any cause, according to Nancy Lin, MD, of the Dana-Farber Cancer Institute in Boston, and colleagues.
They were also more likely to have distant metastases in the brain or lung, but less likely to see the disease recur in bone, Lin and colleagues reported online in Cancer.
The findings come from an analysis of 15,204 women who were diagnosed and treated for stage I through III breast cancer between January 2000 and December 2006 in eight major hospitals that are part of the National Comprehensive Cancer Network centers.
For the analysis, tumors were classified as:

• HR-positive/HER2 negative if they had an estrogen receptor, a progesterone receptor, or both but were negative for human epidermal growth factor receptor 2 (HER2)
• HER2-positive if they had HER2 and any hormone receptor status
• And triple-negative if they had none of the receptors

Analysis of the cohort showed that 17% of women had triple-negative cancers, 17% were HER2-positive, and 66% were HR-positive/HER2 negative.
The triple-negative subtype was nearly twice as common among African-American women, with an adjusted odds ratio of 1.98 (95% CI 1.72 to 2.27, P<0.0001), Lin and colleagues reported.
Only 29% of women with triple-negative cancers were diagnosed as a result of an abnormal screening mammogram, compared with 48% of women with other types, a difference that was significant at P<0.0001.
In an analysis adjusted for age, disease stage, race, tumor grade, and receipt of adjuvant chemotherapy, triple-negative tumors were associated with a greater risk of breast cancer death than receptor-positive tumors.
Specifically, the odds ratio for death over the whole six-year follow-up period was 2.99 (95% CI 2.59 to 3.45).
The odds ratio for death in the first two years after diagnosis, on the other hand, was sharply higher: 8.30 (95% CI 6.23 to 11.05).
The analysis also showed that, compared with women who had receptor-positive tumors, those with triple-negative disease had odds ratios of 2.17, 3.50, and 0.26 for recurrence in the lung, brain, and bone respectively. The differences were all significant at P<0.001.
The researchers cautioned that the analysis was limited to patients at the eight centers, whose median age was 55, younger than the national median.
They also noted that the six-year follow-up was relatively short for HR-positive/HER2 negative and HER2-positive cancers, and "it is likely that survival estimates will evolve over time in this subset."
On the other hand they argued, the picture of outcomes is likely to be accurate for triple-negative cancer, since recurrences were more frequent and earlier.

The study had support from the National Cancer Institute, the National Comprehensive Cancer Network, the Breast Cancer Research Foundation, the American Society of Clinical Oncology, a Berry Junior Faculty Award, and the Karen Webster and David Evans Research Fund.
The journal said the authors made no disclosures.

Primary source: Cancer
Source reference:
Lin NU, et al "Clinicopathologic features, patterns of recurrence, and survival among women with triple-negative breast cancer in the national comprehensive cancer network" Cancer 2012; DOI: 10.1002/cncr.27581.

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Michael Smith
North American Correspondent
North American Correspondent for MedPage Today, is a three-time winner of the Science and Society Journalism Award of the Canadian Science Writers' Association. After working for newspapers in several parts of Canada, he was the science writer for the Toronto Star before becoming a freelancer in 1994. His byline has appeared in New Scientist, Science, the Globe and Mail, United Press International, Toronto Life, Canadian Business, the Toronto Star, Marketing Computers, and many others. He is based in Toronto, and when not transforming dense science into compelling prose he can usually be found sailing.

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 01/03/2013.
This discussion occurred today at Tumor board at the El Paso University Medical Center under the Guidance of  DR Zeina Nahley, MD, FACP, Associate Professor, Chief Division of Hematology/Oncology
at the Paul L. Foster School of Medicine.
CRBCM was represented by DR Kankonde.