Innovative alternative to mastectomy in recurrent breast cancer30 Sep 2016
Treating recurrent breast cancer with a second lumpectomy and partial breast irradiation bring better results than expected compared to conventional breast surgery.
New approach, better results
A recent study focused on this new approach for recurrent breast cancer. In particular, after a median follow-up of 3.6 years, 2 of 58 patients had a second ipsilateral recurrence, and four patients had mastectomy failure, which included the 2 patients with second in-breast recurrence. Both distant metastasis-free (DMFS) and overall survival approached 95%.
The results met or exceeded the trial hypothesis that retreatment with lumpectomy and partial re-irradiation would reduce the 3-year ipsilateral recurrence rate from 25% to 9%, Douglas W. Arthur, MD, of Virginia Commonwealth University in Richmond, reported at the American Society for Radiation Oncology.
"Partial breast re-irradiation with 3D conformal radiation therapy (3DCRT) following second lumpectomy is successful and achieves high local control at 3 years," said Arthur. "We observed minimal late grade 3 treatment-related toxicity and no grade 4 or higher adverse events. This trial adds to the growing data supporting this treatment approach as an alternative to mastectomy."
The findings represented a follow-up report from the prospective, phase 2 RTOG (now NRG) 1014 trial. The trial evaluated the combination of a second lumpectomy, with or without chemotherapy, plus partial breast re-irradiation with 3DCRT as salvage therapy in women who had ipsilateral recurrence after initial breast-conserving therapy for early breast cancer.
Investigators previously reported the primary outcome data, which related to the feasibility and safety of the strategy as an alternative to mastectomy. The initial results showed that repeat lumpectomy and partial breast re-irradiation were associated with acceptable (primarily grade 1/2) skin, breast, and chest adverse events within the first year after completing treatment.
Arthur reported findings related to long-term toxicity, disease control, and survival.
The trial included patients who had breast recurrence more than a year after lumpectomy and whole-breast irradiation for primary, early-stage breast cancer. The patients had unifocal tumors <3cm, negative surgical margins, either negative axillary lymph nodes or no more than three positive nodes without extracapsular extension, no evidence of metastatic spread, and a clearly defined lumpectomy cavity.
Investigators in the trial used a single radiotherapy technique for consistency, maximal homogeneity, wide availability, and data analysis: partial breast re-irradiation with 3DCRT administered in 15 fractions of 1.5 Gy for a total radiation dose of 45 Gy (=unit of absorbed radiation). Arthur said the fractionation scheme had been validated in retreatment of head and neck cancer and shown to be associated with reduced toxicity.
On the basis of available literature, investigators assumed a 3-year ipsilateral recurrence rate and estimated that 55 patients would be required to demonstrate a reduction in the recurrence rate to 9%. Investigators enrolled 65 patients, 58 of whom had complete on-study and adverse-event data.
The patients' original whole-breast irradiation scheme consisted of a median total dose of 50.4 Gy, delivered in a median of 27 fractions. Arthur said 80% of the patients received a radiation boost to the tumor bed.
The patients had a median age of 67 and a median time to ipsilateral recurrence of 13.9 years. Time to recurrence ranged from 1.6 to 27.7 years after initial treatment. The recurrent disease was stage 0 in 22 (37.9%) patients, stage 1 in 35 (60.3%), and stage 2a in one (1.7%) patient.
The histology of the recurrence was invasive ductal in 35 patients and ductal carcinoma in situ in 23. Arthur reported that recurrent disease was estrogen receptor-positive in 44 cases, progesterone receptor-positive in 33 cases, and HER2-positive in 10 cases. In the subset of patients with invasive recurrence, three patients had HER2-positive disease and eight had triple-negative disease.
All patients were clinically node negative, and 44 of the 58 patients had no nodal dissection. The nodal status was pathologically negative in the 14 patients who had sentinel node biopsies, axillary dissections, or both.
With respect to adjuvant systemic therapy, 28 patients received neither chemotherapy nor hormonal therapy, six received chemotherapy, 23 received hormonal therapy, and one patient received both.
The data showed an estimated 3-year in-breast recurrence rate of 3.7% and a mastectomy failure rate of 5.2%. The results met the hypothesized reduction in ipsilateral breast recurrence rate from 25% to at least 9%, said Arthur. Three patients had distant failure and three patients died, resulting in 3-year DMFS and overall survival of 94.8%.
Analysis of late-occurring adverse events showed that most events were grade 1/2 severity (24.1%, 22.4%, respectively). Grade 3 adverse events occurred in 6.9% of patients, the most common being breast disorders. No grade 4/5 adverse events were recorded.
Source: MedPage Today