Lumpectomy May Have Better Survival Than Mastectomy

No Data on Systemic Therapy

Nick Mulcahy

January 28, 2013

Results from the largest-ever observational study of women with early breast cancer "provide confidence" that breast-conserving therapy (BCT) is "an effective alternative" to mastectomy, according to investigators.

In fact, data from 122,000 patients with stage I or II breast cancer, from the California Cancer Registry, suggest that the less invasive BCT, which is a combination of lumpectomy and radiation, provides better survival.

BCT was associated with a superior disease-specific survival at a median follow-up of 110 months (just over 9 years).

BCT was also associated with better overall survival, lead investigator E. Shelley Hwang, MD, MPH, from the Duke Cancer Institute in Durham, North Carolina, and colleagues report in their study, published online today in Cancer.

The investigators analyzed the results by age and hormone-receptor (HR) status, and found that women who were 50 years or older at diagnosis who had HR-positive tumors received the largest disease-specific survival benefit from BCT; they were 14% less likely to die from breast cancer (hazard ratio, 0.86; 95% confidence interval, 0.82 - 0.91). Better disease-specific survival with BCT "was seen among all subgroups analyzed," they report.

Mastectomy is suddenly on the rise in the United States among various populations of women with early breast cancer, the investigators point out.

The results may help women feel more confident about less surgery.

"The study shows that lumpectomy is at least equivalent, if not better, than mastectomy in terms of disease-specific and overall survival," Dr. Hwang told Medscape Medical News. "The results may help women feel more confident about less surgery."

The goal of the study was to learn whether the "equivalent outcomes" seen with BCT and mastectomy in randomized clinical trials hold up in the general population, the investigators note.

They got a surprise. "We observed the unanticipated finding that patients treated with mastectomy had a significantly lower overall survival and breast-cancer-specific survival than women who underwent BCT," they write, adding that they controlled for many variables in the analysis.

Nice Study, But...

Two independent experts asked to comment by Medscape Medical News praised the study, but expressed reservations about the findings.

"This study will be a very useful adjunct to a large body of evidence that shows at least equivalence of the 2 local therapies," said Kandace McGuire, MD, a surgical oncologist at the Magee-Womens Hospital of the University of Pittsburgh Medical Center in Pennsylvania, referring to earlier randomized controlled trials and observational studies.

This study could even be used to "educate patients who do not require mastectomy but choose it for psychologic reasons," she added.

The thought that BCT would lead to improved outcomes does seem counterintuitive.

However, the results give Dr. McGuire pause. "The thought that BCT would lead to improved outcomes does seem counterintuitive," she said, "and may reflect the unmeasured variables."

The unmeasured variables include the use of adjuvant systemic therapy, she explained. "Advances in systemic therapy are credited for a large part of the reduction in mortality from breast cancer we've seen in the past 2 decades."

The absence of data on systemic therapy was especially concerning to another expert.

"We know that systemic therapy has a large influence on overall and disease-specific survival,' said Maurice van der Sangen, MD, a radiation oncologist from Carina Hospital in Eindhoven, the Netherlands, who has studied breast cancer recurrence.

Information about systemic therapy is especially important in this study because there is a "mismatch" between the BCT and mastectomy groups in terms of when they received treatment, he explained.

All of the women in the study population underwent surgery from 1990 to 2004 and were followed at least 5 years (61,771 underwent BCT and 50,383 underwent mastectomy). Notably, the use of mastectomy declined over the study period.

As a result, more women in the mastectomy group than in the BCT group were treated before 1999 (59% vs 48%), when systemic therapy was used only in the case of node-positive disease, said Dr. van der Sangen.

After 1999, systemic therapy was routinely used to treat women with either node-positive or node-negative disease. Thus, the BCT group could have benefited from that extra treatment, and mastectomy could have suffered from the absence of it. "This could be an additional reason for the underperformance of the mastectomy group," Dr. van der Sangen explained.

Dr. McGuire also believes that the mastectomy group might have had less access to healthcare, which can negatively influence outcomes. "It has been described many times in the literature that patients often choose mastectomy over BCT because of lack of access to radiation facilities, either due to distance or socioeconomic status," she said.

Dr. Hwang and her colleagues admit that various unmeasured variables were "likely" to have biased the findings toward higher mortality in women who underwent mastectomy.

One Exception to Benefit

The study population was racially mixed; nearly a quarter of the women were nonwhite. There were 31,416 deaths during the study period, 39% of which were due to breast cancer. Five-year overall survival was 89.3% and 5-year disease-specific survival was 94.4%.

The investigators performed Cox multivariate analysis to compare survival in the 4 groups: HR-negative women 50 years and older; HR-positive women 50 years and older; HR-negative women younger than 50 years; and HR-positive women younger than 50 years.

The analysis controlled for a host of variables, including surgery type, tumor grade, tumor size, proportion of positive lymph nodes, age at diagnosis, year of diagnosis, socioeconomic status, and race.

As noted above, the greatest potential survival benefit was in postmenopausal women 50 years and older with estrogen-receptor-positive T1 tumors. "At least equivalent outcomes" were seen in all groups on multivariable analysis, with the 1 exception — women with tumors 4 to 5 cm. These women "are probably not going to be eligible for lumpectomy anyway because their tumors are too big," Dr. Hwang explained.

Cancer. Published online January 28, 2013. Abstract