In the National Surgical Breast and Bowel Project (NSABP) Trial B-17 at 15 years, the radiation showed a lower rate of ipsilateral invasive recurrence 8.9 versus 19.4 percent, when compared with excision alone [13]. The findings were reported from a large observational study of the Surveillance, Epidemiology, and End Results (SEER) database that included over 100,000 patients; the subgroup of 60,000 women was treated with breast conservation therapy (BCT) with or without radiation being compared with lumpectomy alone. The radiation treatment was associated at 10 years with a lower rate of ipsilateral breast cancer recurrence 2.5 versus 4.9 percent in the lumpectomy. The whole-breast radiotherapy (WBRT) was delivered to the entire breast in 1.8 to 2 Gy daily fractions over 4.5 to 5 weeks to a total dose of 45 to 50 Gy. The women with adjuvant radiation as a component of BCT with an observational study in 1323 women with a median follow-up of 6.6 years suggested that earlier initiation of radiation in ≤ 8 weeks) was associated with a lower incidence of ipsilateral breast tumor recurrence. In two single-institution trials that enrolled a total of 145 women who had undergone breast-conserving surgery for malignancy, patients received accelerated radiation with 41 to 42 Gy delivered over 15 to 16 fractions. In a combined analysis, the recurrence rate at five years was 4 percent, which was similar to the rate of recurrence following WBRT reported in the National Surgical Adjuvant Breast and Bowel Project (NSABP) B-17 trial [13]. Several large, prospective, randomized trials are nearing target accrual or have been completed, including the NSABP/RTOG trial [14], the Milan-based intraoperative radiation trial [15], and the international TARGIT trial [16], and the status of each is discussed. The American Society for Radiation Oncology has also published a consensus statement to guide the use of PBI until randomized, non-inferiority trial done at 97 hospitals [17].
The Danish Breast Cancer Cooperative Group (DBCG) 82 b and c trials have limited addressed the question of whether postmastectomy radiation to the axillary, supra/infraclavicular, and ipsilateral internal mammary nodes improved breast cancer outcomes in pre-and postmenopausal patients, respectively [18, 19]. These studies included node-positive, as well as high-risk, node-negative diseases, which were defined as tumors that were > four to five cm or invaded the skin or fascia. This demonstrated improved disease-free and overall survival associated with radiation among women treated with RT after mastectomy.
It should be noted that the number of patients with node-negative disease was small in the studies with approximately 130 women in each Danish study. The limited data for postmastectomy radiation in triple-negative disease suggest a treatment benefit. The treatment was given to women with triple-negative breast cancer who lack other high-risk features. In a randomized trial of patients with triple-negative breast cancer treated with mastectomy and adjuvant chemotherapy with or without postmastectomy RT, at a median follow-up of 86 months, women who received postmastectomy chest wall RT had significantly better five-year relapse-free survival 88 versus 75 percent and overall survival 90 versus 79 percent when compared with those who received chemotherapy alone [20]. The relapse can occur within two years of primary treatment and distant metastatic disease is already present in 25 to 30 percent of cases. There is 15 to 40 percent of recurrences involve the chest wall and axillary or supraclavicular lymph nodes, breast cancer has the potential to metastasize to almost every organ in the body. The most common sites of metastases are bone, liver, and lung. Approximately 50 to 75 percent of patients who relapse distantly do so in a single organ; the remainder will develop diffuse metastatic disease. Less than 5 percent of patients will manifest central nervous system involvement as the first site of metastatic disease [21].
Given that the prognosis of small, node-negative, triple-negative breast cancers (TNBCs) is generally favorable, the benefit of adjuvant chemotherapy is unclear. In a retrospective review of almost 4400 patients with node-negative pathologic T1 TNBCs, adjuvant chemotherapy was administered in 53 percent of cases [22]. In multivariate analysis, adjuvant chemotherapy improved breast cancer-specific survival in the overall group, but not for patients with T1a tumors, although there were only 18 patients in this subset. We administer adjuvant chemotherapy for patients with node-negative tumors that are ≥ T1b, but typically not for node- negative, T1a TNBCs, although some such patients may reasonably elect for chemotherapy, given limitations in available data.
Neoadjunctive chemotherapy is associated with high rates of clinical response and a greater likelihood of facilitating cosmetically acceptable surgery. Outcomes for patients receiving neoadjuvant versus adjuvant chemotherapy were demonstrated in an individual patient data meta-analysis conducted by the Early Breast Cancer Trialists' Collaborative Group, which was based on data from 4756 women in 10 trials initiated between 1983 and 2002 [23, 24]. The 15-year local recurrence in patients treated with neoadjuvant chemotherapy (21.4% vs. 15.9%; p = 0.0001) compared to adjuvant chemotherapy. No significant difference between the two groups was noted for distant recurrence (38.2% vs. 38.0%; p = 0.45).
Our institution data reveal the control and survival rates for triple negative breast cancers treated by conventional or hypo fraction radiation with neo-adjuvant or adjuvant chemotherapy. In our cohort, balanced arms show that adjuvant chemotherapy is better in clinical outcomes than neoadjuvant chemotherapy. The patients receiving adjunctive chemotherapy had a better 5-year LC, DFS and OS compared to neoadjuvant chemotherapy. The overall rates of neoadjuvant chemotherapy vs. adjuvant chemotherapy are, LC 14.8% vs. 47.9 % (p = 0.002), DFS 24.2% vs. 53.1% (p = 0.015) and OS 65.1% vs. 92.2% (p = 0.002).
It could be hypothesized that the differences in outcomes can be purely due to the more advanced loco-regional disease stage of the neoadjuvant cohort. Yet, in the multivariate analyses, the stage was not a significant factor. Only additional patients and/ or studies from other institutions – prospective or retrospective - can help resolve this contradiction.