T1‑2N1M0 triple‑negative breast cancer patients from the SEER database showed potential benefit from post‑mastectomy radiotherapy
- Authors:
- Published online on: November 21, 2019 https://doi.org/10.3892/ol.2019.11139
- Pages: 735-744
-
Copyright: © Wang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
Abstract
Introduction
Radiotherapy is a significant adjuvant therapy for breast cancer. Post-mastectomy radiation therapy (PMRT) is always recommended for patients at high risk of recurrence, including those with ≥4 positive axial lymph nodes (ALNs) or a tumor >5 cm, independent of the nodal status and resection margins (1). Adjuvant PMRT has been shown to be extremely useful at improving the survival of high-risk patients, however the benefits and demerits of radiotherapy for breast cancer patients have not been established (2).
In 2014, the Early Breast Cancer Trialists' Collaborate Group published a study on the value of PMRT for breast cancer patients (3). The results of that systematic review and meta-analysis of 22 trials demonstrated that PMRT significantly reduced not only the local recurrence rate, but also the breast cancer mortality rate in patients with 1–3 positive ALNs (3). The 2015 European Society for Medical Oncology guidelines recommend PMRT for high-risk patients and also suggest the routine use of PMRT for patients with 1–3 positive ALNs (4). However, the primary limitation of relevant studies is that they were not randomized control studies. Whether patients with Tumor-Node-Metastasis (TNM) stage of T1-2N1M0 require PMRT remains controversial (5,6). T1-2N1M0 refers to: T1-2, maximum tumor diameter ≤50 mm; N1, micrometastasis (maximum diameter >0.2 mm, or >200 tumor cells in a single lymph node tissue section, but the maximum diameter ≤2 mm), 1–3 axillary lymph node metastasis, at least 1 metastatic lesion >2 mm and transfer (including micro transfer); M0, no distant metastasis (7).
In brief, selection of breast cancer patients for PMRT is based on established clinical pathology parameters including the size of the mass and lymph node (LN) status, factors which contribute to the baseline risk of local recurrence (8). Nevertheless, a growing body of data has demonstrated the importance of molecular subtypes in treating patients with breast cancer and predicting their prognoses (9).
Breast cancer has been demonstrated to be a heterogeneous group of diseases (10). Perou et al (11) first discovered the intrinsic subtypes of breast cancer using bioinformatics analysis of gene expression profiling data. The different molecular subtypes of breast cancer have distinct outcomes, and therefore, breast cancer subtypes have been widely used clinically to select adjuvant systemic therapies and predict patient prognosis (12). Comprehensive treatment strategies for breast cancer are based on molecular subtypes, but do not take the individualization of radiotherapy into account (13). There is lack of evidence for making firm recommendations about PMRT in the various breast cancer subgroups. The precise relationship between the intrinsic sensitivity of radiotherapy and the molecular subtypes is not yet known and the mechanisms underlying the different responses of the subtypes have not been elucidated.
As the concept and techniques of genotyping continue to develop, molecular typing has become a standardized treatment for the guidance of chemotherapy and endocrine therapy for patients with breast cancer (14,15). These advances raise the question of whether molecular subtypes can be used to predict the response to PMRT and the prognosis. The present study was conducted to assess the effects of PMRT administered to patients with T1-2N1M0 breast cancer and to evaluate the treatment-predictive effect of breast cancer molecular subtypes among patients in the Surveillance, Epidemiology, and End Results (SEER) registry who underwent PMRT.
Patients and methods
Patient selection
The SEER registry of the National Cancer Institute (USA) is a comprehensive source of information about the occurrence of all new cancer cases among people residing in areas that take part in the SEER program (https://seer.cancer.gov/). Of the 181,878 patients with a pathology-based diagnosis of breast cancer between 2010 and 2013, this study restricted analysis to females with a diagnosis of a single primary and malignant breast neoplasm. The median follow-up time was 34 months (range, 0–59 months). Among these, 2,760 patients were treated with radiotherapy (36.97%; PMRT group). The other 4,706 patients (63.03%) were treated without radiotherapy and were classified as no-PMRT group. As the SEER registry began tracking information regarding HER2/neu status in 2010, this date was used as the earliest period for this study. Inclusion criteria for this study were as follows: i) Diagnosis confirmed by histology; ii) female patients with unilateral breast lesions; iii) mastectomy was performed (surgery of primary site variable values of 50–74); and iv) patients were diagnosed with breast cancer defined as T1-2N1M0 stage, according to the 7th American Joint Committee on Cancer (AJCC) cancer staging manual (7).
The following cases were excluded: i) Patients diagnosed based on an autopsy or death certificate; ii) patients whose PMRT was uncertain; iii) patients who did not undergo a mastectomy; iv) patients with an unknown molecular subtype, unknown age at diagnosis, unknown year of diagnosis, unknown laterality or unknown survival months; and v) patients who received preoperative systemic therapy (radiotherapy and/or chemotherapy). After these exclusions, a total of 7,466 patients were included in the present study for analysis.
Table I represents the demographic variables of the patients selected: Ethnicity (white, black, others); age at diagnosis (<55, ≥55 years); year of diagnosis (2010–2013); and marital status (married, unmarried but domestic partner, unmarried, separated, widowed, divorced, unknown). The cancer characteristics included the following: Laterality (left, right); AJCC T-stage (T1, T2); number of positive LNs (1, 2 or 3); histological type (code 8500/3, infiltrating duct carcinoma; code 8520/3, lobular carcinoma; code 8522/3, infiltrating duct and lobular carcinoma; others); histological grade (well differentiated, moderately differentiated, poorly differentiated, undifferentiated, unknown); hormone receptor (HR) status (positive, negative); and human epidermal growth factor receptor 2 (HER2) status (positive, negative) (Table I).
The treatment characteristics of the patients were chemotherapy (yes, no/unknown) and radiotherapy (PMRT group, no-PMRT group). The tumor molecular subtypes were classified as 4 mutually exclusive categories: HR+/HER2−, HR−/HER2+, HR+/HER2+ and HR−/HER2− [defined as triple-negative breast cancer (TNBC)]. HR+ was defined as estrogen receptor (ER)+, progesterone receptor (PR)+ or borderline positive (those that could not be defined as ER+ or PR+). In contrast, HR− was defined as ER− and PR−. Individuals who had a borderline HER2 status were grouped in another category ‘unknown HER2 status’ (16).
Statistical analysis
The baseline characteristics of the patients were assessed using a Pearsons χ2−test and the aforementioned factors were compared between the PMRT group and the no-PMRT group. The breast cancer-specific survival (BCSS) was extracted from the SEER database. Kaplan-Meier survival curves were generated and the log-rank test was used to identify significant differences between the curves. The prognostic value of PMRT was analyzed by Cox univariate and multivariate regression analyses. Due to the statistical non-significance of the diagnosis year in the univariate regression analysis, this factor was excluded from the multivariate regression analysis. The HR and HER2 statuses of the patients were excluded to avoid a repetition in the analysis. Tests of interaction were used in the Cox multivariate regression analysis. Hazard ratios and 95% confidence intervals (95% CIs) were calculated.
To adjust for potential confounding factors in patients with TNBC, individual propensity score matching (PSM) was performed, in which randomly selected individuals in the PMRT group were paired with comparable individuals in the no-PMRT group. The confounding factors were ethnicity, age, year of diagnosis, marital status, laterality, T stage, positive LN status, histological type, histological grade and chemotherapy. All data analyses were performed using SPSS version 22 (IBM Corp.). All the statistics tests performed were double-sided, and P<0.05 was considered to indicate a statistically significant difference.
Outcome measurement
The main endpoint of this study was 5-year BCSS. The patients were recorded as alive or dead in the SEER database, and the option of ‘completed months of follow-up’ contained the patients survival time in months. The BCSS was calculated from the date of diagnosis to the date of death due to breast cancer or the last follow-up. Patients who were alive were censored on the date of their last visit.
Results
Clinicopathological characteristics of breast cancer patients
A total of 7,466 T1-2N1M0 breast cancer patients treated with a mastectomy were identified from the SEER database. The clinical characteristics of the patients, and the comparison between the PMRT and no-PMRT group are summarized in Table I. As presented in Table I, 65% (n=4,840) of patients were diagnosed after the age of 55 years. Of these 4,840 patients, 32% received PMRT and 68% did not. Analysis of the data also revealed that 68% (n=5,102) of the patients were HR+/HER2−, 6% (n=441) were HR−/HER2+, 14% (n=1,036) were HR+/HER2+ and 12% (n=887) were HR−/HER2− (TNBC). Using the Pearson χ2−test, significant differences were observed between the PMRT and the no-PMRT groups with regard to age at diagnosis (P<0.001), year of diagnosis (P=0.002), marital status (P<0.001), T stage (P<0.001), positive LN (P<0.001), histological grade (P<0.001), HR status (P<0.001), HER2 status (P=0.035), subtype (P<0.001) and chemotherapy (P<0.001) (Table I). Ethnicity (P=0.500), laterality (P=0.353) and histological type (P=0.150) were not significantly different between the PMRT and no-PMRT group (Table I).
Prognostic factors
Univariate and multivariate analyses identified the following independent prognostic factors: Ethnicity (P=0.002; P=0.031); age at diagnosis (P=0.006; P=0.028); T stage (P<0.001; P<0.001); histological grade (P<0.001; P<0.001); molecular subtype (P<0.001; P<0.001); and PMRT (P=0.025; P=0.005) (Table II). The multivariate analysis examining subtypes demonstrated that PMRT was an independent prognostic factor for TNBC (Hazard ratio, 1.519; 95% CI, 1.044–2.208; P=0.029) (Table III).
 | Table II.Univariate and multivariate analysis to evaluate breast cancer-specific survival according to clinicopathological variables from the SEER database. |
Survival analysis
Kaplan-Meier analysis revealed that, among the 4 subtypes of patients with breast cancer, TNBC was associated with the worst BCSS (P<0.001; Fig. 1). Patients with T1-2N1M0 breast cancer treated with PMRT showed improved BCSS compared with those not treated with PMRT (P=0.027; Fig. 2). The Kaplan-Meier analysis of the 4 molecular subtypes revealed that both the HR+/HER2+ (Hazard ratio, 5.208; 95% CI, 4.141–6.550; P=0.025) and HR−/HER2− (Hazard ratio, 3.828; 95% CI, 2.940–4.983; P=0.010) patients benefited from PMRT (Fig. 3). However, no significant statistical difference was observed in the HR+/HER2− (hazard ratio, 0.857; 95% CI, 0.621–1.182; P=0.346) and HR−/HER2+ (hazard ratio, 0.649; 95% CI, 0.292–1.442; P=0.288).
PSM analysis
To decrease the influence of potential confounding factors, a PSM analysis was conducted between the PMRT and no-PMRT group of the 4 molecular subtypes of T1-2N1M0 patients. The Kaplan-Meier analysis after PSM demonstrated that only patients with TNBC benefited from PMRT (hazard ratio, 0.6208; 95% CI, 0.4009–0.9615; P=0.025) while patients with the other 3 molecular subtypes did not (Fig. 4). The PSM analysis assigned 271 patients with T1-2N1M0 TNBC to the PMRT group, matched with 271 patients in the no-PMRT group (Fig. S1). Of the 542 patients with T1-2N1M0 TNBC, no factors differed significantly between the 2 groups (Table IV).
| Table IV.Clinicopathological characteristic before and after PSM in patients with triple-negative breast cancer with and without PMRT. |
Discussion
According to the National Comprehensive Cancer Network (USA), after a patient with breast cancer has undergone a total mastectomy with N2/3 ALNs or a T3/4 primary tumor, PMRT is a standard adjuvant therapy (17). The application of PMRT for T1-2N1M0 breast cancer remains controversial (18–21). The St. Gallen Breast Cancer Conference pointed out that ~64% of experts did not recommend PMRT as a routine treatment for T1-2N1M0 breast cancer (22). Among these experts, 62% agreed that PMRT can be beneficial for patients with adverse prognostic factors (23). In the present study, the molecular subtype of breast cancer was a significant predictor for radiosensitivity.
Breast tumors are heterogeneous, and the heterogeneity determines the strategy for cancer follow-up treatment (24). Previous studies have investigated the relationships between histopathological patterns, including tumor size, histological type and histological grade, and therapy and prognosis (25). Molecular subtypes of cancer are based on gene expression profiling, which reflects the intrinsic nature of the tumor cells (26). Recent studies have demonstrated that these molecular subtypes are associated with different clinical characteristics and outcomes (12,24–29). Due to the high cost of gene expression tests, immunohistochemistry, which is a cheaper alternative, was proposed along with criteria set by the expert panel of the 13th St. Gallen International Breast Cancer Conference (23). However, very few studies of patients with T1-2N1M0 cancer have evaluated the role of molecular subtyping in guiding decisions regarding radiotherapy after mastectomy.
In the Swedish Breast Cancer Group 91 Radiotherapy trial, radiotherapy showed a trend to improve the BCSS for patients with TNBC; however, this trend did not reach significance (30). The results of the present study demonstrated that PMRT can improve the BCSS of patients with T1-2N1M0 TNBC. Of patients with BRCA-1 mutant breast cancer, 60–80% are TNBC, which implies a high association between these types of breast cancer (31). When the BRCA-1 gene is mutated, damaged DNA cannot be repaired by homologous recombination, which is the main method for the repair of double-stranded DNA breaks (31). The dysfunction or deficiency of BRCA-1 may increase the susceptibility to radiotherapy (31).
The main strength of a SEER analysis is that the SEER database has access to a much larger cohort of patients compared with that of a single institution. In the present study, PSM was also conducted to reduce the effects of confounding factors. However, this study had several limitations. Firstly, the SEER registry does not provide any information on the details of treatments such as chemotherapy regimens, HER2-targeted therapy, endocrine therapy or methods of PMRT. In addition, the SEER registry lacks information on the specific positive rates of ER/PR and Ki-67, and therefore, the 4 molecular types examined in this study are only a molecular subtype estimation. Due to HER2 status only being available after 2010 in the SEER database, this resulted in a lack of samples and insufficient follow-up in the present study.
As research on TNBC progresses, patients with the T1-2N1M0 subtype, which has no therapeutic targets to date, may benefit from radiotherapy, although guidelines and current international consensuses do not recommend the routine use of PMRT for patients with this subtype (19,32). Clinical trials should be conducted to validate the effectiveness of radiotherapy after mastectomy in patients with T1-2N1M0 TNBC.
In conclusion, patients with T1-2N1M0 TNBC can benefit from PMRT. Despite limitations, the findings of the current study will help clinicians identify patients with T1-2N1M0 breast cancer who may benefit from PMRT.
Supplementary Material
Supporting Data
Acknowledgements
Not applicable.
Funding
This study was supported by the Jiangsu Natural Science Foundation (grant no. BK20180274).
Availability of data and materials
The datasets generated and/or analyzed during the current study are available in the SSER repository (https://seer.cancer.gov/).
Authors' contributions
XW, YX and LZ made substantial contributions to the conception, design and acquisition of data. SG was involved in collecting data, drafting the manuscript and revising it critically for important intellectual content. YX, SG and MA made substantial contributions to the acquisition, analysis and interpretation of data. LZ, PC, SW, HT and JZ contributed to the data analysis. LZ, SW, PC, MA, HT and JZ revised the manuscript. All authors read and approved the final manuscript.
Ethics approval and consent to participate
Not applicable.
Patient consent for publication
Not applicable.
Competing interests
The authors declare that they have no competing interests.
References
|
Shi W, Luo Y, Zhao D, Huang H and Pang W: Evaluation of the benefit of post-mastectomy radiotherapy in patients with early-stage breast cancer: A propensity score matching study. Oncol Lett. 17:4851–4858. 2019.PubMed/NCBI | |
|
Voduc KD, Cheang MC, Tyldesley S, Gelmon K, Nielsen TO and Kennecke H: Breast cancer subtypes and the risk of local and regional relapse. J Clin Oncol. 28:1684–1691. 2010. View Article : Google Scholar : PubMed/NCBI | |
|
EBCTCG (Early Breast Cancer Trialists' Collaborative Group), ; McGale P, Taylor C, Correa C, Cutter D, Duane F, Ewertz M, Gray R, Mannu G, Peto R, et al: Effect of radiotherapy after mastectomy and axillary surgery on 10-year recurrence and 20-year breast cancer mortality: Meta-analysis of individual patient data for 8135 women in 22 randomised trials. Lancet. 383:2127–2135. 2014. View Article : Google Scholar : PubMed/NCBI | |
|
Senkus E, Kyriakides S, Ohno S, Penault-Llorca F, Poortmans P, Rutgers E, Zackrisson S and Cardoso F; ESMO Guidelines Committee, : Primary breast cancer: ESMO clinical practice guidelines for diagnosis, treatment and follow-up. Ann Oncol. 26 (Suppl 5):v8–v30. 2015. View Article : Google Scholar : PubMed/NCBI | |
|
Whelan TJ, Olivotto IA and Levine MN: Regional nodal irradiation in early-stage breast cancer. N Engl J Med. 373:1878–1879. 2015. View Article : Google Scholar : PubMed/NCBI | |
|
Poortmans PM, Collette S, Kirkove C, Van Limbergen E, Budach V, Struikmans H, Collette L, Fourquet A, Maingon P, Valli M, et al: Internal mammary and medial supraclavicular irradiation in breast cancer. N Engl J Med. 373:317–327. 2015. View Article : Google Scholar : PubMed/NCBI | |
|
Edge SB and Compton CC: The American joint committee on cancer: The 7th edition of the AJCC cancer staging manual and the future of TNM. Ann Surg Oncol. 17:1471–1474. 2010. View Article : Google Scholar : PubMed/NCBI | |
|
Mukesh MB, Duke S, Parashar D, Wishart G, Coles CE and Wilson C: The Cambridge post-mastectomy radiotherapy (C-PMRT) index: A practical tool for patient selection. Radiother Oncol. 110:461–466. 2014. View Article : Google Scholar : PubMed/NCBI | |
|
Valla M, Vatten LJ, Engstrøm MJ, Haugen OA, Akslen LA, Bjørngaard JH, Hagen AI, Ytterhus B, Bofin AM and Opdahl S: Molecular subtypes of breast cancer: Long-term incidence trends and prognostic differences. Cancer Epidemiol Biomarkers Prev. 25:1625–1634. 2016. View Article : Google Scholar : PubMed/NCBI | |
|
Zardavas D, Irrthum A, Swanton C and Piccart M: Clinical management of breast cancer heterogeneity. Nat Rev Clin Oncol. 12:381–394. 2015. View Article : Google Scholar : PubMed/NCBI | |
|
Perou CM, Sørlie T, Eisen MB, van de Rijn M, Jeffrey SS, Rees CA, Pollack JR, Ross DT, Johnsen H, Akslen LA, et al: Molecular portraits of human breast tumours. Nature. 406:747–752. 2000. View Article : Google Scholar : PubMed/NCBI | |
|
Cancer Genome Atlas Network, . Comprehensive molecular portraits of human breast tumours. Nature. 490:61–70. 2012. View Article : Google Scholar : PubMed/NCBI | |
|
Wu CY, Du SL, Zhang J, Liang AL and Liu YJ: Exosomes and breast cancer: A comprehensive review of novel therapeutic strategies from diagnosis to treatment. Cancer Gene Ther. 24:6–12. 2017. View Article : Google Scholar : PubMed/NCBI | |
|
Pusztai L, Broglio K, Andre F, Symmans WF, Hess KR and Hortobagyi GN: Effect of molecular disease subsets on disease-free survival in randomized adjuvant chemotherapy trials for estrogen receptor-positive breast cancer. J Clin Oncol. 26:4679–4683. 2008. View Article : Google Scholar : PubMed/NCBI | |
|
Prat A, Lluch A, Albanell J, Barry WT, Fan C, Chacón JI, Parker JS, Calvo L, Plazaola A, Arcusa A, et al: Predicting response and survival in chemotherapy-treated triple-negative breast cancer. Br J Cancer. 111:1532–1541. 2014. View Article : Google Scholar : PubMed/NCBI | |
|
Howlader N, Altekruse SF, Li CI, Chen VW, Clarke CA, Ries LA and Cronin KA: US incidence of breast cancer subtypes defined by joint hormone receptor and HER2 status. J Natl Cancer Inst. 106:dju0552014. View Article : Google Scholar : PubMed/NCBI | |
|
Gradishar WJ, Anderson BO, Balassanian R, Blair SL, Burstein HJ, Cyr A, Elias AD, Farrar WB, Forero A, Giordano SH, et al: Breast Cancer, Version 4.2017, NCCN clinical practice guidelines in oncology. J Natl Compr Canc Netw. 16:310–320. 2018. View Article : Google Scholar : PubMed/NCBI | |
|
Yin H, Qu Y, Wang X, Ma T, Zhang H, Zhang Y, Li Y, Zhang S, Ma H, Xing E, et al: Impact of postmastectomy radiation therapy in T1-2 breast cancer patients with 1–3 positive axillary lymph nodes. Oncotarget. 8:49564–49573. 2017. View Article : Google Scholar : PubMed/NCBI | |
|
Nordenskjold AE, Fohlin H, Albertsson P, Arnesson LG, Chamalidou C, Einbeigi Z, Holmberg E, Nordenskjöld B and Karlsson P; Swedish Western and Southeastern Breast Cancer Groups, : No clear effect of postoperative radiotherapy on survival of breast cancer patients with one to three positive nodes: A population-based study. Ann Oncol. 26:1149–1154. 2015. View Article : Google Scholar : PubMed/NCBI | |
|
Chitapanarux I, Tharavichitkul E, Jakrabhandu S, Klunklin P, Onchan W, Srikawin J, Pukanhaphan N, Traisathit P and Vongtama R: Real-world outcomes of postmastectomy radiotherapy in breast cancer patients with 1–3 positive lymph nodes: A retrospective study. J Radiat Res. 55:121–128. 2014. View Article : Google Scholar : PubMed/NCBI | |
|
He ZY, Wu SG, Zhou J, Li FY, Lin Q, Lin HX and Sun JY: Postmastectomy radiotherapy improves disease-free survival of high risk of locoregional recurrence breast cancer patients with T1-2 and 1 to 3 positive nodes. PLoS One. 10:e01191052015. View Article : Google Scholar : PubMed/NCBI | |
|
Gnant M, Harbeck N and Thomssen C: St. Gallen/Vienna 2017: A brief summary of the consensus discussion about escalation and de-escalation of primary breast cancer treatment. Breast Care (Basel). 12:102–107. 2017. View Article : Google Scholar : PubMed/NCBI | |
|
Goldhirsch A, Winer EP, Coates AS, Gelber RD, Piccart- Gebhart M, Thürlimann B and Senn HJ; Panel members, : Personalizing the treatment of women with early breast cancer: Highlights of the St gallen international expert consensus on the primary therapy of early breast cancer 2013. Ann Oncol. 24:2206–2223. 2013. View Article : Google Scholar : PubMed/NCBI | |
|
Chen HL, Ding A and Wang FW: Prognostic effect analysis of molecular subtype on young breast cancer patients. Chin J Cancer Res. 27:428–436. 2015.PubMed/NCBI | |
|
Shen H, Zhao L, Wang L, Liu X, Liu X, Liu J, Niu F, Lv S and Niu Y: Postmastectomy radiotherapy benefit in Chinese breast cancer patients with T1-T2 tumor and 1–3 positive axillary lymph nodes by molecular subtypes: An analysis of 1369 cases. Tumour Biol. 37:6465–6475. 2016. View Article : Google Scholar : PubMed/NCBI | |
|
Wang J, Shi M, Ling R, Xia Y, Luo S, Fu X, Xiao F, Li J, Long X, Wang J, et al: Adjuvant chemotherapy and radiotherapy in triple-negative breast carcinoma: A prospective randomized controlled multi-center trial. Radiother Oncol. 100:200–204. 2011. View Article : Google Scholar : PubMed/NCBI | |
|
Moo TA, McMillan R, Lee M, Stempel M, Ho A, Patil S and El-Tamer M: Impact of molecular subtype on locoregional recurrence in mastectomy patients with T1-T2 breast cancer and 1–3 positive lymph nodes. Ann Surg Oncol. 21:1569–1574. 2014. View Article : Google Scholar : PubMed/NCBI | |
|
Abdulkarim BS, Cuartero J, Hanson J, Deschênes J, Lesniak D and Sabri S: 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. 29:2852–2858. 2011. View Article : Google Scholar : PubMed/NCBI | |
|
Nguyen PL, Taghian AG, Katz MS, Niemierko A, Abi Raad RF, Boon WL, Bellon JR, Wong JS, Smith BL and Harris JR: Breast cancer subtype approximated by estrogen receptor, progesterone receptor, and HER-2 is associated with local and distant recurrence after breast-conserving therapy. J Clin Oncol. 26:2373–2378. 2008. View Article : Google Scholar : PubMed/NCBI | |
|
Sjöström M, Lundstedt D, Hartman L, Holmberg E, Killander F, Kovács A, Malmström P, Niméus E, Werner Rönnerman E, Fernö M and Karlsson P: Response to radiotherapy after breast-conserving surgery in different breast cancer subtypes in the swedish breast cancer group 91 radiotherapy randomized clinical trial. J Clin Oncol. 35:3222–3229. 2017. View Article : Google Scholar : PubMed/NCBI | |
|
Cleator S, Heller W and Coombes RC: Triple-negative breast cancer: Therapeutic options. Lancet Oncol. 8:235–244. 2007. View Article : Google Scholar : PubMed/NCBI | |
|
Yu T and Di G: Role of tumor microenvironment in triple-negative breast cancer and its prognostic significance. Chin J Cancer Res. 29:237–252. 2017. View Article : Google Scholar : PubMed/NCBI |
