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ORIGINAL ARTICLE
Year : 2019  |  Volume : 15  |  Issue : 5  |  Page : 1031-1034

Does addition of postmastectomy radiotherapy improve outcome of patients with pT1-2, N0 triple negative breast cancer as compared to breast conservation therapy?


1 Department of Radiation Oncology, Regional Cancer Centre, Trivandrum, Kerala, India
2 Department of Cancer Epidemiology and Biostatistics, Regional Cancer Centre, Trivandrum, Kerala, India

Date of Web Publication4-Oct-2019

Correspondence Address:
Rajeev Kavalakara Raghavan
Department of Radiation Oncology, Regional Cancer Centre, Trivandrum - 695 011, Kerala
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/jcrt.JCRT_974_17

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 > Abstract 


Background: Triple-negative breast cancers (TNBCs) form a heterogeneous group of cancers typically exhibiting an aggressive behavior resulting in increased risk of locoregional relapse (LRR) and distant metastases. The effect of radiotherapy on LRR risk and overall survival (OS) in women treated with mastectomy alone for early-stage TNBC remains unclear.
Aim: The aim of this study is to compare the locoregional recurrence rate, disease-free survival (DFS), and OS following breast conservation therapy (BCT) or modified radical mastectomy (MRM) alone in women with stage I and IIA TNBC and to assess the impact of tumor and treatment-related factors.
Materials and Methods: Patients with early-stage (pT1-2, N0) TNBC-treated between January 1, 2010, and December 31, 2011, were identified from the hospital-based registry records. The mean age was 48 years. Forty-nine patients underwent BCT, and 121 underwent MRM. The majority of the patients in both groups had T2 and grade 3 disease. None of the patients had margin positive status after surgery. Five patients had lymphovascular invasion (LVI).
Results: At a median follow-up of 50 months (range: 4–83 months), there was no locoregional recurrence (LRR) in either arm. Eight patients relapsed, six developed distant metastases, and one patient each had a new primary in the contralateral breast and ovary. Two patients died of disseminated cancer, one each in the BCT and MRM groups. The five-year DFS was 95.8% and 91.1% for the BCT group and MRM group, respectively, (P = 0.83). The corresponding 5-year OS was 98% and 97.5% (P = 0.527). There was no statistically significant difference in outcome based on age, grade, LVI, or margin status between both groups.
Conclusion: This retrospective analysis identified no statistically significant difference in outcome regarding LRR, DFS, or OS in patients treated without adjuvant radiation for women with pT1-T2N0 TNBC who underwent MRM in comparison to BCT.

Keywords: Breast conservation therapy, modified radical mastectomy, triple-negative breast cancer


How to cite this article:
Raghavan RK, Ibrahim S, Jagathnath Krishna K M, Mathew BS. Does addition of postmastectomy radiotherapy improve outcome of patients with pT1-2, N0 triple negative breast cancer as compared to breast conservation therapy?. J Can Res Ther 2019;15:1031-4

How to cite this URL:
Raghavan RK, Ibrahim S, Jagathnath Krishna K M, Mathew BS. Does addition of postmastectomy radiotherapy improve outcome of patients with pT1-2, N0 triple negative breast cancer as compared to breast conservation therapy?. J Can Res Ther [serial online] 2019 [cited 2019 Nov 13];15:1031-4. Available from: http://www.cancerjournal.net/text.asp?2019/15/5/1031/244244




 > Introduction Top


Triple-negative breast cancers (TNBCs) are heterogeneous tumors with distinct molecular features and are phenotypically characterized by the absence of estrogen and progesterone receptor expression and human epidermal growth factor receptor 2 gene amplification. Typically, of ductal histology, larger size, higher grade, high-proliferative index, high mitotic rates, and early lymph node involvement, these are aggressive tumors resulting in a poor prognosis. Nevertheless, the current locoregional treatment recommendations for TNBC follow similar principles as of other molecular subtypes - stage for stage. Retrospective data suggest the risk of LRR in high risk (grade 3 and lymphovascular invasion [LVI]) node-negative patients after modified radical mastectomy (MRM) is approximately 20% irrespective of the breast cancer subtype.[1] A single-institution retrospective data reported the absolute reduction of LRR risk by 6% in T1-2N0 TNBC treated with breast conservation surgery (BCS) plus radiotherapy (BCT) compared with MRM alone, suggesting a benefit of radiotherapy although there was no overall survival (OS) benefit.[2] The effect of radiotherapy on LRR risk and OS in women treated with mastectomy alone for early-stage TNBC remains unclear. This Institutional Review Board approved retrospective analyses were conducted to compare the LRR rate, disease-free survival (DFS), and OS following BCT and MRM in patients with early-stage (pT1-2N0) TNBC and to assess the impact of other tumor and treatment-related factors on outcome.


 > Materials and Methods Top


Women who were treated at Regional Cancer Centre, Trivandrum, between January 1, 2010, and December 31, 2011, with a diagnosis of pT1-T2, N0 TNBC, were identified through the hospital's cancer registry. The medical case records were reviewed, and the patients' demography, tumor, treatment, and follow-up-related details were collected in a structured manner. A total of 196 patients were identified. Of these 26 patients who had received postmastectomy radiotherapy (PMRT) were excluded from this analysis.

The primary outcome measures assessed were LRR (defined as the first site of tumor recurrence – ipsilateral chest wall [local] and/or axillary, supraclavicular or infraclavicular, and internal mammary nodes), DFS, and OS were defined as time from the date of diagnosis to the date of the last follow-up or mortality due to any cause. Survivors were censored at the date of the last contact.

Statistical analysis

The distributions of patient, tumor, and treatment characteristics (including age, tumor size and grade, presence of LVI, and receipt of chemotherapy) by the status of treatment – BCT versus MRM – were compared using Chi-square or Fisher's exact tests, as appropriate. Survival curves were estimated using the Kaplan–Meier method and compared by the log-rank test. The analysis was done using SPSS 20, (IBM, Armonk, NY, United States of America).


 > Results Top


The mean age of the evaluable group (170 patients) was 48 years (range: 26–71 years). The majority of the patients in both groups had pT2 and grade 3 disease. Forty-nine patients underwent BCT, and 121 patients underwent MRM. Five patients had LVI. None had margin positive status after surgery. The median number of dissected nodes were 15 (range: 1–30). Seventy-seven patients (45.3%) received both adriamycin- and taxane-based chemotherapy, 63 patients (37%) received adriamycin-based regime (AC/FEC/FAC), 26 (15.3%) received taxane-based regime (TC), and four (2.4%) patients did not receive chemotherapy. None of the patients received neoadjuvant chemotherapy. The tumor and treatment characteristics for BCS and MRM are given in [Table 1]. The characteristics, patient's age (P = 0.0007), and menstrual status (P = 0.0002) show statistical significance between BCS and MRM. Patients who underwent BCS received whole-breast radiation using the three-dimensional conformal technique to a total dose of 40 Gy in 15 fractions followed by boost to the surgical bed to a dose of 10 Gy in five fractions.
Table 1: Patient and tumor characteristics

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The median follow-up of all patients was 50 months (range: 4–83 months). None of the patients developed locoregional relapse in either group. Six patients developed distant metastasis (five in the MRM group and one in the BCT group). Two patients (one in each group) died of disseminated cancer; two patients developed new primary (ovary and leukemia), one in each group. Five-year DFS rates were 91.1% and 95.8% for MRM and breast conservation therapy (BCT) groups, respectively, (P = 0.83) [Figure 1]. Five-year OS was 97.5% for patients who underwent mastectomy alone as compared to 98% for those who underwent BCT (P = 0.527) [Figure 2]. There was no statistically significant difference in outcome based on age, grade, LVI, margin status, or use of anthracycline- and taxane-based chemotherapy regimens.
Figure 1: The survival difference in type of surgery based on disease-free survival

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Figure 2: The survival difference in type of surgery based on overall survival

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 > Discussion Top


In general, for all patients with invasive carcinoma of the breast received breast-conserving therapy, those who underwent mastectomy with tumor >5 cm or with positive margins, those underwent mastectomy with positive axillary nodes require adjuvant radiation therapy. There are currently no tumor subtype-specific guidelines regarding adjuvant radiation therapy. Haffty et al. demonstrated that individuals with TNBC were more likely to have a locoregional failure, in comparison to distant metastasis.[3] Dent et al. showed the incidence of locoregional recurrence in TNBC patients peaks during years 1–4, but then sharply declines.[4]

There is relative radioresistance of the TNBC subtype as a consequence of the estrogen receptor (ER)-negative status. ER expression results in a decrease in cell-cycle duration and reduces the time available for the repair of DNA damage caused by radiation. It was suggested that ER-negative cells as found in TNBC and basal-like breast cancer would thus exhibit radioresistance, as DNA repair is allowed to progress during the slower cell cycle.[5] However, there have been several retrospective studies analyzed the role of radiation therapy in TNBC, but their findings are conflicting.[6],[7] Gabos et al. did not find an increased risk of locoregional recurrence associated with TNBC in patients receiving BCS; however, an increased risk was seen in patients who received MRM and who had TNBC (Hazard ratio 4.72, 95% confidence interval 1.53–14.52, P = 0.0069).[8] This indicated a need for further study to determine the risk of locoregional recurrence in patients also receiving PMRT.

There has been a recent interest in determining the benefit of radiation for pT1-2 node-negative patients. The results of these trials are conflicting, and the survival implication of PMRT in pT1-T2 tumors and negative nodes is unclear. Abdulkarim et al. found that T1-2N0 TNBC patients treated with MRM without RT had a significantly increased risk of locoregional recurrence in comparison with those treated with BCT; however, there was no difference in OS.[2] Kyndi et al. in their study of high-risk patients who underwent MRM, the authors found no survival benefit for PMRT in patients with TNBC.[7]

This study shows the impact of adjuvant radiation therapy in patients with T1-2, N0 TNBC. The primary aim was to compare the LRR rate, DFS, and OS following BCT and MRM in this subgroup of patients. With a median follow-up of 50 months (range: 4–83 months), there was no statistically significant difference in LRR, DFS, or OS in two subgroups. These observations corroborate those documented by Kyndi et al. in their study of high-risk patients who underwent MRM.[7] No statistically significant difference in outcome based on age, grade, LVI, margin status, or use of taxane-based and nontaxane-based chemotherapy regimens observed between both of these groups. The current study has limitations as a retrospective study.


 > Conclusion Top


There was no increase in locoregional relapse following MRM without adjuvant radiation therapy for women with pT1-T2N0 TNBC in comparison to BCT. Both DFS and OS at 5 years were similar in MRM and BCT group. No differences could be detected among the groups based on the known tumor or treatment-related prognostic factors. Prospective, randomized trials including more patients and longer follow-up are required before use of routine PMRT in this subset of patients.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
 > References Top

1.
Truong PT, Lesperance M, Culhaci A, Kader HA, Speers CH, Olivotto IA. Patient subsets with T1-T2, node-negative breast cancer at high loco regional recurrence risk after mastectomy. Int J Radiat Oncol Biol Phys 2005;62:75-182.  Back to cited text no. 1
    
2.
Abdulkarim BS, Cuartero J, Hanson J, Deschênes J, Lesniak D, Sabri S, et al. Increased risk of locoregional recurrence for women with T1-2N0 triple-negative breast cancer treated with modified radical mastectomy without adjuvant radiation therapy compared with breast-conserving therapy. J Clin Oncol 2011;29:2852-8.  Back to cited text no. 2
    
3.
Haffty BG, Yang Q, Reiss M, Kearney T, Higgins SA, Weidhaas J, et al. Locoregional relapse and distant metastasis in conservatively managed triple negative early-stage breast cancer. J Clin Oncol 2006;24:5652-7.  Back to cited text no. 3
    
4.
Dent R, Trudeau M, Pritchard KI, Hanna WM, Kahn HK, Sawka CA, et al. Triple-negative breast cancer: Clinical features and patterns of recurrence. Clin Cancer Res 2007;13:4429-34.  Back to cited text no. 4
    
5.
Panoff JE, Hurley J, Takita C, Reis IM, Zhao W, Sujoy V, et al. Risk of loco regional recurrence by receptor status in breast cancer patients receiving modern systemic therapy and post mastectomy radiation. Breast Cancer Res Treat 2011;128:899-906.  Back to cited text no. 5
    
6.
Dragun AE, Pan J, Rai SN, Kruse B, Jain D. Locoregional recurrence in patients with triple-negative breast cancer: Preliminary results of a single institution study. Am J Clin Oncol 2011;34:231-7.  Back to cited text no. 6
    
7.
Kyndi M, Sørensen FB, Knudsen H, Overgaard M, Nielsen HM, Overgaard J, et al. Estrogen receptor, progesterone receptor, HER-2, and response to postmastectomy radiotherapy in high-risk breast cancer: The Danish breast cancer cooperative group. J Clin Oncol 2008;26:1419-26.  Back to cited text no. 7
    
8.
Gabos Z, Thoms J, Ghosh S, Hanson J, Deschênes J, Sabri S, et al. The association between biological subtype and locoregional recurrence in newly diagnosed breast cancer. Breast Cancer Res Treat 2010;124:187-94.  Back to cited text no. 8
    


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