Breast-conserving surgery led to improved cancer-specific survival in early breast cancer as compared with mastectomy, with or without radiation therapy, a large retrospective review showed.

Patients treated with breast conservation had significantly higher 5- and 10-year survival, including an 11% absolute difference from mastectomy plus radiation therapy at 10 years, according to Jayant Agarwal, MD, of the University of Utah in Salt Lake City, and co-authors.

After controlling for differences among patient groups, breast conservation was associated with a 30% improvement in survival versus mastectomy alone, increasing to 47% versus mastectomy plus radiation therapy, they reported in JAMA Surgery.

"Our analysis of a large and contemporary cohort of patients demonstrates that patients who undergo breast-conserving therapy have improved breast cancer-specific survival compared with patients who undergo mastectomy alone or mastectomy with radiation for early-stage invasive ductal carcinoma," concluded.

"The finding of improved survival with breast-conserving therapy in this large database study could be due to differences in adjuvant therapy regimens or tumor biology. These findings deserve investigation to determine which factors may be contributing to this effect."

Another large review published in the journal showed that women with triple-negative breast cancer did not have a higher risk of locoregional recurrence with breast conservation than with mastectomy.

Earlier Studies Found No Difference

Long-term follow-up in two large randomized clinical trials (RCTs) showed no difference in survival in patients with early breast cancer treated with breast-conserving surgery plus radiation therapy versus mastectomy with or without adjuvant radiation. Several smaller trials with briefer follow-up also showed no survival difference with the two types of surgery.

Some of the landmark trials were initiated more than 40 years ago. No recent randomized trials have compared breast conservation and mastectomy in contemporary patient populations, the authors noted.

To determine whether conservative and radical surgery still lead to similar outcomes, Agarwal and colleagues analyzed data from the National Cancer Institute's Surveillance, Epidemiology, and End Results program. They searched for patients treated during 1998 to 2008 for early breast cancer, defined as tumor size ≤4 cm and three or fewer positive lymph nodes.

The search identified 132,149 patients, 70% of whom were treated with breast-conserving therapy, 27% with mastectomy alone, and 3% with mastectomy plus radiation therapy. The primary outcome was breast cancer-specific mortality.

The analysis yielded a 5-year breast cancer-specific survival of 97% with breast conservation, 94% with mastectomy alone, and 90% with mastectomy plus radiotherapy (P<0.001). The 10-year results continued to show a significant advantage for breast-conserving treatment: 94%, 90%, and 83%, respectively (P<0.001).

Multivariate analysis produced a survival hazard ratio of 1.31 for breast conservation versus mastectomy alone (P<0.001) and 1.47 for mastectomy plus radiotherapy (P<0.001). A propensity-matched analysis did not substantively change the results.

RCTs Versus Observational Studies

An RCT still trumps an observational study, and data from RCTs have shown that breast-conservation and mastectomy lead to similar outcomes in patients with early breast cancer, said Adam Brufsky, MD, PhD, of the University of Pittsburgh.

RCTs employ methods to ensure that patients assigned to different treatment groups have similar characteristics. Well-balanced RCTs have shown no difference between breast-conserving therapy and mastectomy.

"[The authors] acknowledge that people who got mastectomy or mastectomy with radiation may have had more aggressive biology not accounted for in their multivariate model," Brufsky told MedPage Today. "They don't really explain why they think that doesn't matter."

The most likely explanation is that patients in the mastectomy group had more aggressive and more extensive disease in the breast, for which mastectomy is usually the approach in the modern era of breast cancer treatment, Brufsky added.

Triple-Negative Study

Breast-conserving treatment has a controversial history in triple-negative disease. Because of its aggressive phenotype and absence of molecular targets for novel systemic therapies, some breast cancer authorities have considered triple-negative disease a relative contraindication to breast-conserving surgery.

"For patients with triple-negative breast cancer who undergo breast-conserving therapy, many investigators suggest that local recurrence, regional recurrence, and distant metastasis are increased and that overall survival is decreased compared with the outcomes of patients with non-triple-negative subtypes," Armando Giuliano, MD, of Cedars-Sinai Medical Center in Los Angeles, and co-authors noted in their introduction.

To examine the validity of concerns about increased recurrence risk and decreased survival, the authors analyzed records of patients treated for breast cancer at Cedars-Sinai from Jan. 1, 2000, through May 30, 2012. They excluded male breast cancer patients, patients who received neoadjuvant chemotherapy, and patients with <90 days of follow-up.

The records revealed 1,851 patients who underwent breast-conserving surgery and for whom complete data were available for estrogen-receptor, progesterone-receptor, and HER2 status.

The authors determined that 234 patients (12.6%) had triple-negative breast cancer, 1,341 (72.4%) had luminal A subtype, 212 (11.5%) had luminal B subtype, and 64 (3.5%) had HER2-positive cancers. Three-fourths of the patients were >50, and the luminal A group was slightly older (60 versus 56 to 57 for the other subgroups).

All but 5% of the patients had stage I (60.6%) or stage II (34.6%) disease at presentation. Patients with triple-negative disease were younger (56.1 versus 59.6, P<0.001) and had larger tumors (2.1 versus 1.8 cm, P<0.001). Triple-negative breast cancer tended to be high grade, stage II or III versus I, and infiltrating ductal histologic type (P<0.001).

Overall, half the patients received chemotherapy and 91% received radiotherapy. Patients with triple-negative and HER2-positive disease were more likely to get chemotherapy (85% versus 65% for luminal B and 38% for luminal A).

Local and Distant Recurrence

A total of 47 patients had local recurrence, including 11 (4.7%) in the triple-negative group, eight (12.5%) in the HER2 group, 23 (1.7%) in the luminal A patients, and 4 (1.9%) with luminal B. Estimated freedom from local recurrence at 5 years was 93% with triple-negative breast cancer versus 95% to 96% for the other groups (P=0.13).

The authors identified 21 regional recurrences: three (1.3%) in the triple-negative group, four (6.3%) in the HER2 group, nine (0.7%) in the luminal A group, and five (2.4%) in the luminal B group. Estimated freedom from regional recurrence at 5 years was significantly lower in the HER2 group (84%) versus the other three groups (96% to 98%, P<0.001).

Distant recurrence was the most common type of recurrence, as 66 patients who underwent breast-conserving surgery developed metastatic breast cancer. Distant recurrence rates were 9.0% (N=21) in the triple-negative group, 7.8% (N=5) in the HER2 group, 2.3% (N=31) in the luminal A patients, and 4.2% (N=9) in the luminal B patients.

The estimated 5-year freedom from distant recurrence was 85% with triple-negative disease, 88% with HER2-positive disease, 95% for luminal A cancers, and 92% for luminal B cancers (P<0.001). Triple-negative disease conferred a higher risk of distant recurrence as compared with the luminal A subtype (HR 2.5, P=0.001).

The authors found that 113 patients died. Triple-negative breast cancer was associated with worse survival as compared with luminal A (HR 3.5, P<0.001) and luminal B (HR 3.7,P=0.001) subtypes.

"Triple-negative breast cancer is associated with worse overall survival and an increased risk for distant recurrence," the authors concluded. "However, this study validates the lack of a significant risk for local recurrence in triple-negative breast cancer patients who undergo breast-conserving therapy.

"Despite the aggressive nature of triple-negative breast cancer, the triple-negative phenotype does not lead to a significantly increased risk of loco-regional recurrence compared with the non-triple-negative breast cancer phenotype in patients undergoing breast-conserving therapy. Breast-conserving therapy is appropriate for triple-negative breast cancer and should be routinely offered."

The study by Giuliano and co-authors was supported by the Fashion Footwear Charitable Foundation of New York, Associates for Breast and Prostate Cancer Studies, Avon Foundation, Margie and Robert E. Petersen Foundation, and Linda and Jim Lippman.

Agarwal and co-authors disclosed no relevant relationships with industry.

Giuliano and co-authors disclosed no relevant relationships with industry.