Postmastectomy Radiotherapy In Breast Cancer Patients Research Articles

Hypofractionated Postmastectomy Radiotherapy (HF-PMRT): What did We Learn from COVID-19 Era?

Objectives: In breast cancer (BC) patients receiving mastectomy, postmastectomy radiotherapy (PMRT) improves long-term outcomes by decreasing local failure and cancer mortality. However, the optimal PMRT schedule is still under investigation. The present review aims to discuss the evidence regarding hypofractionated (HF) PMRT in BC patients in order to identify the optimal treatment approach. Additional purpose is to highlight what we have learned from COVID-19 era regarding HF schedules for PMRT in BC patients. Mechanism: Between February and November 2021, literature and database research were conducted. Key references were detected from a PubMed query. Range of publication date was between 2000 and 2021. Selection criteria included English language publications in humans. Hand searching included meeting proceedings of the European Society for Radiotherapy and Oncology (ESTRO), European Society of Medical Oncology (ESMO), American Society of Clinical Oncology (ASCO) and American Society for Radiation Oncology (ASTRO). The website clinicaltrials.gov was also searched. Randomized controlled trials evaluating HF-PMRT were included. Findings in brief: Our research returned 87 published papers. Fourteen trials were included in our final analysis. The comparisons of several different schedules of HF-PMRT with conventional fractionated PMRT provided similar results in terms of locoregional disease control without increasing toxicity. Particularly, an acute skin toxicity incidence grade 2 or higher ranged between 10 and 25% among the studies we analyzed. Conclusions: The present paper suggests that safety and efficacy of HF-PMRT is comparable with conventional schedules and standard practice guidelines are already available. COVID-19 pandemic has emphasised the need for increasingly tailored treatment protocols. Modern HF regimens should continue to be the standard of treatment in BC patients who receive PMRT also in the post-COVID-19 era.

Tumor-infiltrating lymphocytes predict improved overall survival after post-mastectomy radiotherapy: a study of the randomized DBCG82bc cohort

Background The predictive value of tumor-infiltrating lymphocytes (TILs) on the benefit from radiotherapy (RT) remains unclear. Our aim was to investigate the association between TILs and post-mastectomy RT (PMRT) regarding the risk of recurrence and survival in a randomized cohort. Material and methods Stromal TILs were histologically estimated in 1011 tumors from high-risk breast cancer (BC) patients from the DBCG82bc trial. Patients were diagnosed between 1982 and 90, treated with total mastectomy and partial axillary lymph node dissection, randomized to ± PMRT followed by adjuvant systemic treatment. A competing risk model, Kaplan–Meier analysis and multivariate Cox regression analysis were used for correlating TILs and clinical outcome. Results 106 of 1011 patients (10.5%) showed high TILs using a 30% cut-off. In multivariate regression analysis, a high level of TILs was an independent factor associated with lower risk of distant metastasis (DM) and improved overall survival (OS), but without association with loco-regional control. High TILs were associated with a significantly greater OS after PMRT at 20 years compared to low TILs (8% improvement for low TILs (23% to 31%) vs. 22% for high TILs (26% to 48%), interaction-test: p = 0.028). The association between TILs and PMRT was more pronounced among estrogen-receptor negative (ER–) tumors, and patients having ER–/low TILs tumors showed no OS benefit from PMRT at 20 years (–4% improvement for low TILs (28% to 24%) vs. 23% for high TILs (20% to 43%). A similar trend in the association between high TILs and reduced risk of DM after PMRT was seen. Conclusion High TILs predict improved OS from PMRT in BC patients, and the association appeared especially strong for ER– tumors. A trend in the association between high TILs and reduced risk of DM after PMRT was seen. These findings may indicate that RT triggers an immune response inducing a systemic effect outside the treatment field.

Optimal Reconstruction Type and PMRT Timing for Breast Cancer Patients treated by Neoadjuvant Chemotherapy and Mastectomy.

The challenge for locally advanced breast cancer patients who receive neoadjuvant chemotherapy followed by mastectomy with reconstruction and post mastectomy radiotherapy (PMRT), is the timely delivery of PMRT without jeopardizing either reconstruction aesthetics outcomes or tumor control. We aim to explore the most favorable reconstruction type in this unique patient population We reviewed the charts of 1,791 breast cancer patients who underwent breast reconstruction with either Autologous flaps (AR) or Two Stages expander/implant (TE/I) or Single Stage permanent implant (PI) from 2000-2017. Among these patients, 294 received neoadjuvant chemotherapy and PMRT. The primary endpoint was to detect the association between the reconstruction type and reconstruction complications as infection, skin necrosis and fat necrosis. Subgroup analysis was performed for patients with implant-based reconstruction to compare (PI) to (TE/I) in terms of capsular contracture, implant rupture, implant exposure and overall implant failure defined as removal of implant or expander regardless the replacement outcome. The secondary endpoint was to explore the timing interval between immediate implant reconstruction and PMRT associated with lesser probability of implant failure. Logistic regression and Polynomial regression were used to assess the primary and secondary endpoints respectively. Median follow-up was 94 months for the entire cohort. Thirty-one percent (90/294) had AR, 29% (85/294) had TE/I and 40% (118/294) had PI. Two percent of AR recipients developed infection compared to 6% in PI and 14% in TE/I, while there was no significant difference between three groups in terms of skin necrosis and fat necrosis. Multivariate analysis revealed that TE/I was associated with significantly higher risks of infection (OR: 3.3, p=0.02) compared to single stage, while there was no significant difference between PI and AR (OR: 0.5, p=0.3). Subgroup analysis revealed that there was no significant difference between PI and TE/I in terms of capsular contracture (7% vs 9%, p=0.8), implant exposure (2% vs 5%, p=0.1) and implant rupture (0% vs 0.2%). 15% of PI recipients experienced reconstruction failure compared to 34% in TE/I group (OR: 2.8, p<0.01). This difference was also significant on multivariate level (OR: 2.7, P=0.012). The median wait time for PMRT delivery was 8 weeks in PI recipients and 10 weeks in TE/I (p=0.02). Timing interval regression analysis showed that PMRT at 2 months for PI was associated with lowest probability of complications (10%) vs (25%) for TE/I. The lowest probability of complications for TE/I patients (15%) is expected at 5 months post reconstruction. Single stage reconstruction in PMRT settings following neoadjuvant chemotherapy, offers less complications in comparison to two stages reconstruction. Also, Single stage reconstruction enhances the timely delivery of PMRT in breast cancer patients receiving neoadjuvant chemotherapy.

Receipt of radiotherapy after mastectomy in women with breast cancer: Population-based cohort study in New Zealand.

To investigate the receipt of postmastectomy radiotherapy (PMRT) in breast cancer patients in New Zealand for whom radiotherapy is strongly recommended in current clinical guidelines. This study involved all women who were diagnosed with primary invasive breast cancer in two health regions, had undergone a mastectomy, and met the "strong recommendation" criteria for PMRT based on New Zealand National Guidelines. We performed logistic regression analyses to identify demographic and clinical factors associated with the receipt of PMRT. Of the 1455 patients with stage II to III cancers included in this analysis, 1195 (82%) received radiotherapy. The receipt of PMRT decreased with increasing age, and was significantly lower in rural residents, Māori and Pacific women, those with more comorbidity, those who received primary cancer care in a public facility, and those diagnosed with stage III cancer. Although not significant, the receipt was also lower in patients who resided in more deprived neighborhood, and those with comorbidities. The findings restricted to stage III patients (n=1325), and to those diagnosed since 2010 (n=422), after the current guidelines were published, which were very similar to the whole cohort. Disparities exist in the receipt of PMRT in breast cancer patients in New Zealand, underscoring the need for a greater equity focus in management of breast cancer.

Abstract P2-11-11: Role of postmastectomy radiotherapy after neoadjuvant chemotherapy in breast cancer patients: A study from the Japanese breast cancer registry

Abstract Background: Postmastectomy radiotherapy (PMRT) has been shown to be beneficial in node-positive breast cancer patients. However, the role of PMRT for patients receiving modern neoadjuvant chemotherapy (NAC) are controversial. We aimed to evaluate the efficacy of radiotherapy for breast cancer patients treated with NAC and mastectomy in the Japanese Breast Cancer Registry. Methods: Patients who received NAC and mastectomy for cT1-4 cN0-2 M0 breast cancer were included in this analysis. We assessed locoregional recurrence (LRR), distant disease-free survival (DDFS), and overall survival (OS) using the Kaplan-Meier method and compared them between the groups with and without PMRT by nodal status after NAC; ypN0, ypN1, and ypN2-3. We also performed multivariable cox regression analysis to evaluate the association of radiotherapy and these outcomes adjusting for baseline patient and cancer characteristics. Results: Of the 145,530 patients registered from 2004 to 2009, we identified 3,226 patients who met our inclusion criteria with the 5-year follow-up information including 1,299 ypN0, 1,036 ypN1, and 879 ypN2-3 cases. PMRT was performed in 185 patients (14.2%) with ypN0, 265 patients (25.6%) with ypN1, and 543 patients (61.8%) with ypN2-3. There was no difference in LRR, DDFS, and OS between the groups with and without radiotherapy for ypN1 patients who received NAC (P=0.72, P=0.29, and P=0.36, respectively). For patients with ypN2-3 breast cancer, radiotherapy significantly improved LRR (P&amp;lt;0.001), DDFS (P=0.01), and OS (P&amp;lt;0.001) on univariate analysis. No difference in LRR, DDFS, and OS was observed for ypN0 patients (P=0.81, P=0.15, and P=0.05, respectively). In multivariable analysis, the use of radiotherapy was independently associated with improved LRR [hazard ratio (HR): 0.608, 95% confidence interval (CI): 0.452–0.818, P=0.001] and OS [HR: 0.685, 95% CI: 0.531–0.885, P=0.004] for ypN2-3 patients. Effect of PMRT on locoregional recurrence by the ypN subgroupsypN subgroupHazard ratio95%CI Low95%CI HighP valueypN00.8550.4581.5960.623ypN10.8320.5491.2620.387ypN2-30.6080.4520.8180.001 Effect of PMRT on overall survival by the ypN subgroupsypN subgroupHazard ratio95%CI Low95%CI HighP valueypN01.3250.8412.0870.224ypN10.8800.5991.2930.514ypN2-30.6850.5310.8850.004 Radiotherapy was not associated with OS among patients with ypN0 [HR: 1.325, 95% CI: 0.841–2.087, P=0.224] and ypN1 [HR: 0.880, 95% CI: 0.599–1.293, P=0.514]. There was no significant difference in DDFS with the addition of radiotherapy for all ypN subgroups. Conclusions: The results from this nationwide database study of breast cancer patients following modern NAC showed that PMRT did not improve survival for patients with ypN1 and ypN0. Radiotherapy might be only beneficial for ypN2-3 breast cancer patients who received NAC and mastectomy in the modern era. Randomized clinical trials are needed to optimize the use of PMRT for breast cancer patients treated with neoadjuvant chemotherapy. Citation Format: Miyashita M, Niikura N, Kumamaru H, Miyata H, Ishida T, Kinoshita T, Tsuda H, Nakamura S, Tokuda Y. Role of postmastectomy radiotherapy after neoadjuvant chemotherapy in breast cancer patients: A study from the Japanese breast cancer registry [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P2-11-11.

A prognostic score model to determine which breast cancer patients with 1-3 positive lymph nodes after modified radical mastectomy should receive radiotherapy.

There is no consensus on the indication for postmastectomy radiotherapy (PMRT) in breast cancer patients with one to three positive lymph nodes. To identify patients for whom PMRT may be indicated, we used a prognostic score model with the SEER database to retrospectively analyze 8049 patients with one to three positive lymph nodes who underwent mastectomy with or without PMRT between 2010 and 2013. Kaplan-Meier analysis showed that PMRT patients had better overall survival (OS) than no-PMRT patients (P < 0.001); however, there was no difference in cancer-specific survival (CSS) (P = 0.530). Multivariate analysis with Cox regression showed that grade (P < 0.001), tumor size (P < 0.001), and progesterone receptor status (P < 0.001) were independent prognostic factors for OS. To diminish bias, we used 1:1 propensity score matching analysis and prognosis score model, which revealed that PMRT patients had better OS and CSS than no-PMRT patients (P < 0.001). In a concrete subgroup analysis of PMRT patients, significant improvements in OS were observed in patients scoring 0, 1, or 2. PMRT patients scoring 2 also had improved CSS. The magnitude of the OS and CSS difference with PMRT correlated with the prognostic score (P < 0.001). These results suggest PMRT in breast cancer patients with one to three positive lymph nodes should be based on patient factors, tumor biology, and prognostic score.

Better survival in PMRT of female breast cancer patients with >5 negative lymph nodes: A population-based study.

Many studies have confirmed the role of postmastectomy radiotherapy (PMRT) for breast cancer patients with at least 4 lymph nodes invasion in the postoperative therapy. Recently, the number of negative lymph nodes (NLNs) has been increasingly paid attention to and recognized as a prognostic indicator in different kinds of caners. Therefore, it is very necessary to study the association between the number of NLNs and the prognosis of PMRT in breast cancer patients. In our study, we used Surveillance, Epidemiology, and End Results (SEER) population-based data and identified 16,686 breast cancer patients to explore their correlation. The ROC curve and the log-rank χ test were applied to determine the appropriate cutoff point of the number of NLNs and 5 was selected as the cutoff point. Furthermore, the cutoff point 5 was validated as an independent prognostic factor affecting cancer-specific survival (CSS) and overall survival (OS) in breast cancer patients, as confirmed by both univariate and multivariate analysis (P < 0.001). In addition, subgroup analysis showed that the number of NLNs >5 can be a prognostic indicator in patients with PMRT according to different clinical variables (all, P < 0.001). Importantly, our results showed that PMRT obviously improved CSS and OS in patients regardless of the number of NLNs (P < 0.001). In conclusion, our study showed the number of NLNs is an independent prognostic factor for breast cancer patients with PMRT, and those who have higher number of NLNs have an increased CSS and OS.