Breast conserving therapy (BCT) may offer better survival rates over mastectomy to women with early-stage, hormone-receptor positive disease, according to research from MD Anderson Cancer Center.
The study findings defy the conventional belief that the two treatment interventions offer equal survival, and show the need to revisit some breast cancer practice standards.
The research was presented at the 2014 Breast Cancer Symposium by Catherine Parker, M.D., formerly a fellow at MD Anderson, now at the University of Alabama at Birmingham.
In the 1980s, both US-based and international randomized clinical studies found that BCT and mastectomy offered women with early-stage breast cancer equal survival benefit. However, those findings come from a time when very little was understood about breast cancer biology, explains Isabelle Bedrosian, M.D., associate professor in Surgical Oncology at MD Anderson.
“Forty years ago, very little was known about breast cancer disease biology — such as subtypes, differences in radio-sensitivities, radio-resistances, local recurrence and metastatic potential,” explains Bedrosian, the study’s senior author. “Since then, a whole body of biology has been learned — none of which has been incorporated into patient survival outcomes for women undergoing BCT or a mastectomy.”
Bedrasian and fellow researchers thought it was important to visit the issue of BCT versus mastectomy in the context of tumor biology.
With tumor biology considered, the researchers hypothesized that patients’ surgical choice would impact survival.
For the retrospective, population-based study, the researchers used the National Cancer Database (NCDB), a nationwide outcomes registry of the American College of Surgeons, the American Cancer Society and the Commission on Cancer that captures approximately 70% of newly diagnosed cases of cancer in the country. They identified 16,646 women in 2004-05 with Stage I disease who underwent mastectomy, breast-conserving surgery followed by six weeks of radiation (BCT), or breast-conserving surgery without radiation (BCS). Since estrogen receptor (ER) and progesterone receptor (PR) data were available and HER2 status was not, the researchers categorized the tumors as ER or PR positive (HR positive), or both ER and PR negative (HR negative). Patients were rigorously matched using propensity-score for a broad range of variables — including age, receiving hormone therapy and/or chemotherapy, as well as type of center where patients were treated, and co-morbidities.
Of the 16,646 women: 1,845 (11%) received BCS; 11,214 (67%) received BCT and 3,857 (22%) underwent a mastectomy. Women who had BCT had superior survival to those who had a mastectomy or BCS — the five-year overall survival was 96%, 90% and 87%, respectively. After adjusting for other risk factors, the researchers again found an overall survival benefit for BCT compared to BCS and mastectomy. In a matched cohort of 1,706 patients in each arm, the researchers still found an overall survival benefit with BCT over mastectomy in the HR positive subset, but not in the HR negative subset.
While provocative, Bedrosian cautions that the findings are not practice changing, as the study is retrospective. Still, the research complements other recent studies that showed BCT was associated with a survival benefit compared to mastectomy. Also, she points to the delivery of radiation therapy as the possible driver of the overall survival benefit.
“We’ve historically considered surgery and radiation therapy as tools to improve local control,” says Bedrosian. “Yet recent studies suggest that there are survival-related benefits to radiation in excess of local control benefits. Therefore, radiation may be doing something beyond just helping with local control. Also, we know hormone receptive positive tumors are much more sensitive to radiation, which could explain why we found the survival benefit in this group of patients.”
As follow up, Bedrosian and her team hope to mine the randomized controlled trial findings from the 1980s, matching those cohorts to current NCDB patients to see if a similar survival benefit could be observed.
“While retrospective, I think our findings should give the breast cancer community pause. In the future, we may need to reconsider the paradigm that BCT and mastectomy are equivalent,” she says. “When factoring in what we know about tumor biology, that paradigm may no longer hold true.”
Barriers to breast-conserving surgery
Though breast-conserving therapy has been the standard of care in treating early-stage breast cancer for almost 25 years, barriers to BCT still exist for certain patients, with some still opting for a mastectomy, according to research from MD Anderson.
The study found that barriers are socioeconomic, rather than medically influenced. Meeghan Lautner, M.D., formerly a fellow at MD Anderson, now at The University of Texas at San Antonio, presented the findings at the 2014 Breast Cancer Symposium.
BCT for early-stage breast cancer includes breast conserving surgery, followed by six weeks of radiation. It has remained the accepted standard of care for early-stage breast cancer since 1990, when clinical trials confirmed its efficacy and the National Institutes of Health issued a consensus statement. Yet, a number of patients still opt for a mastectomy. The MD Anderson researchers set out to determine why.
For their retrospective, population-based study, the researchers used the National Cancer Database — a nationwide outcomes registry of the American College of Surgeons, the American Cancer Society and the Commission on Cancer that captures approximately 70% of newly diagnosed cancer cases. They identified 727,927 women diagnosed with early-stage breast cancer between 1998 and 2011, all who had undergone either BCT or a mastectomy.
Overall, the researchers found that BCT rates increased from 54 percent in 1998 to 59 percent in 2006, and stabilized since then. Adjusting for demographic and clinical characteristics, BCT was most common in women ages 52 to 61 who had private insurance, a higher education level and median income, and who were treated at an academic medical center, versus a community medical center. Geographically, BCT rates were higher in the Northeast than in the South, and in women who lived within 17 miles of a treatment facility compared to those who lived farther away.
“What’s particularly novel and most meaningful about our study is that we looked at how the landscape has changed over time,” says Bedrosian, the study’s senior author. “We hope this will help us understand where we are and are not making progress, as well as identify the barriers we need to overcome to create equity in the delivery of care for our patients.”
Bedrosian is gratified to see that in the areas where physicians and the medical field can make a direct impact — such as geographic distribution and practice type — disparities have equalized over time. However, she notes that factors outside the influence of the medical field, such as insurance type, income and education, still remain. Of great interest is the insurance disparity, says Bedrosian.
“Now with healthcare exchanges providing new insurance coverage options, will we rectify the disparity and overall increase BCT use? We’ll have wait to see,” she says.