Study details
In recent years, there has been increased diagnosis of multiple foci of ipsilateral breast cancer, Dr. Boughey said in her presentation. “This is both as a result of improvements in screening imaging, as well as diagnostic imaging and an increased use of preoperative breast MRI.”
Although historical, retrospective studies have shown high rates of local regional recurrences with breast-conserving therapy in women with more than one foci of breast cancer, more recent analyses have indicated that the approach is associated with “acceptable” recurrence rates.
This, Dr. Boughey explained, is due not only to improvements in breast imaging but also to better pathologic margin assessment, and improved systematic and radiation therapy.
Nevertheless, “most patients who present with two or three sites of cancer in one breast are recommended to undergo a mastectomy,” she noted.
To examine the safety of breast-conserving therapy in such patients, the team conducted a single-arm, phase 2 trial in women at least 40 years of age who had two or three foci of breast cancer, of which at least one site was invasive disease.
“While a randomized trial design would have provided stronger data, we felt that accrual to such a design would be problematic, as many patients and surgeons would not be willing to randomize,” Dr. Boughey explained.
Participants were required to have at least 2 cm of normal tissue between the lesions and disease in no more than two quadrants of the breast. They could have node-negative or N1 disease.
Women were excluded if they had foci > 5 cm on imaging; had bilateral breast cancer; had known BRCA1/2 mutations; had had prior ipsilateral breast cancer; or had received neoadjuvant therapy.
All women in the trial underwent lumpectomy with nodal staging, with adjuvant chemotherapy at the physician’s discretion, followed by whole-breast irradiation, with regional nodal irradiation again at the physician’s discretion. This was followed by systemic therapy, at the discretion of the medical oncologist.
The women were then followed up every 6 months until 5 years after the completion of whole-breast irradiation.
Details of the results
Dr. Boughey said that previously presented data from this study revealed that 67.6% of women achieved a margin-negative excision in a single operation, whereas 7.1% converted to mastectomy. The cosmetic outcome was rated as good or excellent at 2 years by 70.6% of women.
For the current analysis, a total of 204 women were evaluable, who had a median age of 61.1 years. Just over half (59.3%) had T1 stage disease, and 95.6% were node-negative. The majority (83.5%) had ER+/HER2- breast cancer, whereas 5.0% had ER-/HER2- disease and 11.5% had HER2+ positive tumors.
Adjuvant chemotherapy was given to 28.9% of women, whereas 89.7% of those with ER+ disease received adjuvant endocrine therapy.
The primary outcome was local recurrence rate at 5 years, which had a prespecified acceptable rate of less than 8%.
Dr. Boughey showed that, in their series, the 5-year recurrence rate was just 3.1% (95% confidence interval [CI], 1.3%-6.4%), which was “well below” the predefined “clinically significantly threshold.” This involved four cases in the ipsilateral breast, one in the skin, and one in the chest wall.
In addition to the six women with local regional recurrence, six developed contralateral breast cancer and four patients developed distant disease. There were no cases of local and distant recurrence. There were three non–breast cancer primary cancers: one gastric, one lung, and one ovarian.
Eight women died during follow-up; only one of the deaths was related to breast cancer.
Dr. Boughey explained that the small number of local recurrences was too small to identify predictive factors via multivariate analysis.
However, univariate analysis indicated that there were numerical but nonsignificant associations between local recurrence and pathologic stage T2-3 disease, pathologic nodal involvement, and surgical margins just under the negative threshold.
Among the 10 cases of ER–/HER2– breast cancer, there was one local recurrence, giving a 5-year rate of 10.0% vs. 2.6% for women with ER+/HER2– disease.
To examine the role of MRI, Dr. Boughey highlighted that although the imaging modality was initially a requirement for study entry, an amendment to the protocol in 2015 allowed 15 women who had not had MRI to take part.
The local recurrence rate in women who had undergone MRI was 1.7% vs. 22.6% in those who had not, for a hazard ratio of 13.5 (P = .002).
“While this was statistically significant, we need to bear in mind that this was a secondary unplanned analysis,” Dr. Boughey underlined.
Next, the team analyzed the impact of adjuvant endocrine therapy in the 195 women with at least one ER+ lesion, finding that it was associated with a 5-year recurrence rate of 1.9% vs. 12.5% in those who did not receive endocrine therapy, for a hazard ratio of 7.7 (P = .025).
Dr. Boughey highlighted that the study is limited by being single-arm and having only a small subset of patients without preoperative MRI, with HER2+ or ER–/HER2– disease, and with three foci of disease.
She also emphasized that “there is concern that the 5-year follow up on this protocol may be shorter than needed,” especially in women with ER+ disease.
The study was supported by the National Institutes of Health. Dr. Boughey declared relationships with Eli Lilly and Company, Symbiosis Pharma, CairnSurgical, UpToDate, and PeerView.
A version of this article first appeared on Medscape.com.