By Annette M. Boyle

Military Women Have Higher Rates, Lower Survival
SAN ANTONIO, TX — Metastatic breast cancer remains incurable, but new research presented at the CTRC-AACR San Antonio Breast Cancer Symposium indicates that eribulin mesylate, already approved by the Food and Drug Administration for refractory breast cancer, may be as effective as standard therapy in earlier lines of treatment. The research provides some good news for active duty and veteran women, who have increased risk of breast cancer and lower survival rates than their civilian sisters.

An earlier trial showed eribulin to be “the first cytotoxic agent to have survival benefit in women with heavily pretreated metastatic breast cancer,” said lead researcher Peter A. Kaufman, MD, associate professor of medicine at the Geisel School of Medicine at Dartmouth and the Norris Cotton Cancer Center in Lebanon, NH, in his presentation. Eribulin is an anti-microtubule agent with a distinctive method of action. 1

The randomized, prospective international phase III trial enrolled 1,102 patients in a comparison of eribulin to capecitabine in first, second, and third-line settings. All patients previously had received taxane and anthracycline-based therapies.

While the study did not demonstrate superiority of eribulin over capecitabine, “there was a numerical trend favoring eribulin,” noted Kaufman. The median survival for patients receiving eribulin was 15.9 months, compared with 14.5 for those in the capecitabine group. Progression-free survival rates were essentially the same for both groups at 4.1 months and 4.2 months, respectively.

Preplanned subgroup analysis showed that two groups seemed to derive particular benefit from treatment with eribulin: Patients with triple negative breast cancer, a particularly aggressive subtype that currently can only be treated by chemotherapy, had improved overall survival of about five months (14.4 versus 9.4 months) on eribulin compared to capecitabine; and patients with HER2-negative breast cancer also had improved overall survival on eribulin at 15.9 months, compared with those on capecitabine at 13.5 months. Kaufman and colleagues plan additional research on the drug’s effectiveness in those subtypes.

Kaufman noted that the trial did not obtain its primary endpoint of statistical superiority, “but with a study of this size, certainly I feel it demonstrates activity of eribulin in this patient population and activity that compares quite favorably to a widely used standard of care” in earlier treatment of metastatic breast cancer.

Adverse effects were consistent with the known side-effects of both eribulin and capecitabine: neutropenia (54% vs. 16%), hand-foot syndrome (.2% vs. 45%), alopecia (355 vs. 4%), leucopenia (31% vs. 10%), diarrhea (14% vs. 29%), and nausea (22% vs. 24%), respectively.

Higher Incidence in Military Women
Developing more options for treatment of breast cancer at all stages is of increasing importance to the Department of Defense and Veterans Administration, with the rise in the number of women they treat.  Women are expected to account for more than 10% of veterans by the end of this decade and already compose nearly 20% of active-duty forces. Among both groups, breast cancer is more prevalent and has lower survival rates than seen in the general population.

Women on active duty have significantly increased incidence of breast cancer, compared with civilians, according to a comparison of the Department of Defense’s Automated Central Tumor Registry (ACTUR) and the National Cancer Institute’s Surveillance Epidemiology and End Results (SEER) database.

Among white women in the service, breast cancer occurs at the rate of 36.44 cases for every 100,000 people, compared with 30.62 for every 100,000 civilians, a nearly 20% increase. Among black women, the breast cancer rates for active-duty women are 37% higher than among civilians, at 45.87 and 32.54 in 100,000, respectively. 2

A high percentage of African-American (40%) and Hispanic (10%) women on active duty also makes developing treatment options for metastatic cancer increasingly important for the DoD.

“Death rates from breast cancer tend to be particularly high in these ethnic groups, owing in part to later stage of detection and to the more-aggressive nature of breast cancer in these groups,” according to the Clinical Breast Care Project at Walter Reed National Military Medical Center , Bethesda, MD.

Lower Survival Rates for Veterans
An informal VA study showed that “the stage at which breast cancer was diagnosed was higher in the VA than outside, but we are not clear why that is,” Michael Kelley, MD, national program director for oncology told U.S. Medicine.

According to an analysis of the VA cancer survival registry done presented by Ramya Thota and colleagues at the 2010 American Society of Clinical Oncology Breast Cancer Symposium, female veterans are diagnosed with breast cancer about five years earlier than nonveteran women (age 56 vs. 61) and have lower five-year survival rates at every stage when compared to women in the SEER database. 3

Thota’s team analyzed records of 3,815 female VHA patients diagnosed between 1995 and 2009. They found that, among those diagnosed with breast cancer at Stage 1, the five-year survival rate for veteran women was 86.65% vs. 98% in the general population; at Stage 2, it was 79.79% vs. 83.6%. Female veterans diagnosed at Stage 3 had a 60% five-year survival rate, while women in the general population had an 83.6% survival rate; and at Stage 4, the rates were 35% vs. 57.9%.

While breast cancer occurs In men, it remains extremely rare, with about 2,000 cases diagnosed per year, according to the American Cancer Society.

In recent years, the VA aggressively has stepped up screening for breast cancer and is now “better at screening for breast cancer and all cancers,” than any other organization in the country, and “we are committed to making sure that those who are diagnosed receive state of the art care,” Kelley said.

For veterans at risk of metastatic breast cancer, Kelley notes that the VA uses the Oncotype DX test to help determine which early-stage patients are more likely to relapse and assess the likely benefit from adjuvant chemotherapy. “The extensive use of this expensive test is a testament to the VA’s commitment to break down financial barriers to providing appropriate care for all our veterans.”

1. Kaufman PA, Awada A, Twelves C, et al: A phase III, open-label, randomized, multicenter study of eribulin mesylate versus capecitabine in patients with locally advanced or metastatic breast cancer previously treated with anthracyclines and taxanes. 2012 San Antonio Breast Cancer Symposium. Abstract S6-6. Presented December 7, 2012.

2. Zhu K, Devesa S, Wu H, Zahm SH, Jatoi I, et al. Cancer incidence in the U.S. military population: Comparison with rates from the SEER program. Cancer Epidemiol Biomarkers prev. 20009 June:18(6):1740-1745.

3. Thota R, Subbiah S, Tashi T, Aldoss I. Breast cancer in female veteran population: Survival analysis from VA cancer registry. ASCO 2010 Breast Cancer Symposium.