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Study Suggests Viable Alternative to Mastectomy After In-Breast Recurrence

— Mastectomy rates low, good cancer control in selected patients

MedpageToday

A second lumpectomy followed by partial breast re-irradiation (PBrI) was an effective alternative to mastectomy in women who had in-breast cancer recurrence after initial treatment with breast-conserving surgery and whole breast irradiation (WBI), a single-center, phase II study found.

At a median follow-up of 5.5 years (range, 0.1-7.2 years), there were only four second, in-breast recurrences among the first 55 patients re-treated, for a 3-year cumulative incidence of second, in-breast recurrences of 3.4% (95% CI, 0.6%-10.7%), reported Douglas Arthur, MD, of Virginia Commonwealth University in Richmond, and colleagues. The 5-year cumulative incidence of second in-breast recurrences was 5.2% (95% CI, 1.4%-13.2%).

"Continued follow-up of patients enrolled in the NRG/RTOG 1014 trial demonstrated that a second breast-conservation approach using lumpectomy and partial breast re-irradiation for management of in-breast recurrence was associated with continued high breast preservation (5-year freedom from mastectomy rate of 90%), with good cancer control and low risk of toxic effects," the researchers wrote in .

They noted that approximately 10% of 10 women treated with lumpectomy and irradiation will have a recurrence of breast cancer in the ipsilateral breast -- i.e., in-breast recurrence -- which historically, has always been managed with mastectomy.

An from the same trial indicated that in the first 55 evaluable patients, grade 1 adverse events (AEs) occurred in 64% of the group, grade 2 AEs occurred in 7%, and grade 3 occurred in less than 2%; there were no grade 4 or 5 AEs reported.

In the updated analysis, Arthur and co-authors focused on effectiveness end points as well as any further AEs occurring more than a year after completion of therapy. A total of 58 evaluable patients were treated with a second lumpectomy followed by three-dimensional, conformal, external-beam partial breast re-irradiation, where patients received 1.5 Gy twice a day for a total dose of 45 Gy in 30 fractions to the defined partial breast target.

Treatment was delivered during 15 consecutive working days with each fraction separated by a minimum of 6 hours, and "mastectomy failure" was considered in the context of the cumulative incidence of mastectomy performed for any reason, the team explained.

Patients' mean age was 65.1 years, and the majority were white; 60% of the group had invasive histologic subtypes, and the remaining 40% had ductal carcinoma in situ (DCIS).

"In-breast recurrences were discovered early; therefore, most were small, with an invasive median tumor size of 1.0 cm (range, 0.2-2.5 cm) and a DCIS median tumor size of 1.0 cm (range 0.2-3.0 cm)," the investigators reported, adding that 7% of the invasive cancers were ERBB2 positive and 23% were triple negative; all patients had clinically node-negative disease.

Of the 58 evaluable patients, four (7%) received chemotherapy, 22 (38%) had hormonal therapy, two (3%) had both, and 30 (52%) received neither.

Seven patients underwent mastectomy of the treated breast; four of the mastectomies were performed for in-breast recurrences, while two others were done for treatment of nonhealing wounds. The seventh procedure was done as a bilateral mastectomy to treat a contralateral breast cancer.

The 5-year cumulative incidence of mastectomy was 10% (95% CI, 4%-20%), while both the distant metastasis-free survival and overall survival rates at 5 years were 95% (95% CI, 85%-98%). AEs that occurred more than a year after the completion of partial breast re-irradiation were grade 1 in 25% of the group, grade 2 in 26%, and grade 3 in 7%; breast skin and fibrosis changes were the most common AEs.

"The NRG Oncology/RTOG 1014 trial outcomes demonstrated that a second lumpectomy with partial breast re-irradiation was associated with high rates of breast preservation, low rates of second local regional recurrence, and acceptable toxic effects," Arthur and colleagues concluded.

They cautioned, however, that this approach is not recommended for all patients with an in-breast recurrence after their first lumpectomy but rather only for women with small, recurrent disease amenable to a second lumpectomy and who are motivated to avoid a mastectomy.

Carefully Selected Patients

Writing in an , Kiri Cook, MD, of Oregon Health and Science University in Portland, and Maggie DiNome, MD, of the University of California, Los Angeles, said the study provides "important and compelling" data to justify this treatment approach in carefully selected patients.

"Women who are relatively low risk, such as those in this patient population (i.e., small tumors, mostly hormone receptor positive, and with a long interval from first diagnosis [median of 13.4 years in this study]) are likely to have durable long-term control and survival with second breast conservation therapy with PBrI," Cook and DiNome stated. They agreed, however, that the results cannot be extrapolated to all patients with in-breast recurrent cancer, since women in the study were older, with a median age of 67, and almost all were white.

"Some may posit that a 3-week course of twice-daily radiotherapy is too burdensome for patients," the editorialists continued. Although the treatment does represent a significant commitment in time, "it is likely that women who are interested in breast conservation despite knowing that mastectomy is another treatment option would be more willing to accept the inconvenience, especially because options for reconstruction after mastectomy in the postirradiation setting are more limited."

Disclosures

Arthur reported having no conflicts of interest; several co-authors reported various disclosures.

Cook and DiNome reported having no financial disclosures.

Primary Source

JAMA Oncology

Arthur DW, et al "Effectiveness of breast-conserving surgery and 3-dimensional conformal partial breast reirradiation for recurrence of breast cancer in the ipsilateral breast. The NRG Oncology/RTOG 1014 phase 2 clinical trial" JAMA Oncol 2019; DOI: 10.1001/jamaoncol.2019.4320.

Secondary Source

JAMA Oncology

Cook K, DiNome M "Additional lumpectomy and irradiation for in-breast recurrence of cancer -- when less is more" JAMA Oncology 2019; DOI: 10.1001/jamaoncol.2019.4319.