Which real indications remain for mastectomy?

The study of He et al. compared outcomes after breast-conserving therapy including radiation therapy with mastectomy without radiation therapy, after preoperative systemic therapy for patients with early stage HER2-positive breast cancer.1He X. Ji J. Qdaisat A. Esteva F.J. Yeung S.C.J. Long-term overall survival of patients who undergo breast-conserving therapy or mastectomy for early operable HER2-positive breast cancer after preoperative systemic therapy: an observational cohort study.Lancet Reg Health Am. 2024; 32100712https://doi.org/10.1016/j.lana.2024.100712Summary Full Text Full Text PDF Scopus (0) Google Scholar After a median follow-up of 9.9 years, breast-conserving therapy was associated with significantly higher overall survival compared to mastectomy (86.0% vs 79.3%; P = 0.02). This difference was significant for patients who had a pathological complete response in axillary lymph nodes (91.3% vs 83.5%, P = 0.02) and for those with a pathological complete response in the breast (93.4% vs 87.0%, P = 0.03), although the latter result was not significant in multivariable analysis. The authors hypothesise that the better survival outcomes after breast-conserving therapy may be explained by the impact of radiation therapy on the microenvironment, and/or that more extensive surgery negatively impacted on the immune response or directly caused local, vascular or lymphatic seeding. We fully agree that the interactions between surgery, radiation therapy, systemic treatments, and the immune environment require further research. More than 20 years ago, pivotal randomised trials unambiguously demonstrated the non-inferiority of breast-conserving therapy compared to mastectomy for women with early breast cancer. Modestly higher local recurrence rates after breast-conserving therapy were well-balanced by similar long-term overall survival and an improved quality of life. Over the last decades, multidisciplinary breast cancer management has improved tremendously, and local recurrence rates after breast-conserving therapy have fallen markedly. Most observational studies since then reported improved outcomes following breast-conserving therapy compared to mastectomy.2Lagendijk M. van Maaren M.C. Saadatmand S. et al.Breast conserving therapy and mastectomy revisited: breast cancer-specific survival and the influence of prognostic factors in 129,692 patients.Int J Cancer. 2018; 142: 165-175Crossref PubMed Scopus (117) Google Scholar, 3de Boniface J. Szulkin R. Johansson A.L.V. Survival after breast conservation vs mastectomy adjusted for comorbidity and socioeconomic status: a Swedish national 6-year follow-up of 48 986 women.JAMA Surg. 2021; 156: 628-637Crossref PubMed Scopus (114) Google Scholar, 4Landercasper J. Ramirez L.D. Borgert A.J. et al.A reappraisal of the comparative effectiveness of lumpectomy versus mastectomy on breast cancer survival: a propensity score-matched update from the National Cancer Data Base (NCDB).Clin Breast Cancer. 2019; 19: e481-e493Summary Full Text Full Text PDF PubMed Google Scholar An EBCTCG meta-analysis comparing preoperative systemic therapy with postoperative systemic therapy suggested that patients receiving preoperative systemic therapy and breast-conserving therapy might have increased local recurrence rates compared to those receiving postoperative systemic therapy, although survival was identical.5Long-term outcomes for neoadjuvant versus adjuvant chemotherapy in early breast cancer: meta-analysis of individual patient data from ten randomised trials.Lancet Oncol. 2018; 19: 27-39Summary Full Text Full Text PDF PubMed Scopus (712) Google Scholar The randomized trials included were historic and current thinking is that there should be no concerns about higher local recurrence rates in contemporary care. Indeed, a more recent analysis of the SEER database using propensity score matching of 4890 patients treated with preoperative systemic therapy between 2010 and 2020 reported significantly worse overall survival and BCSS outcomes after mastectomy compared to breast-conserving therapy.6Zhang M. Sun Y. Wu H. et al.Prognostic analysis of cT1-3N1M0 breast cancer patients who have responded to neoadjuvant therapy undergoing various axillary surgery and breast surgery based on propensity score matching and competitive risk model.Front Oncol. 2024 24; 141319981Google Scholar However, despite increasing pathological complete response rates with modern treatments, this didn't translate into increasing use of breast-conserving therapy, even in HER2-positive disease with a likelihood of more than 60% of obtaining a pathological complete response.7Criscitiello C. Golshan M. Barry W.T. et al.Impact of neoadjuvant chemotherapy and pathological complete response on eligibility for breast-conserving surgery in patients with early breast cancer: a meta-analysis.Eur J Cancer. 2018; 97: 1-6Summary Full Text Full Text PDF PubMed Scopus (36) Google Scholar Opinions vary concerning how much statistical techniques, including propensity score matching or inverse probability treatment weighting, can mitigate the effects of the confounding that is inherent in observational research.8van Maaren M.C. le Cessie S. Strobbe L.J.A. Groothuis-Oudshoorn C.G.M. Poortmans P.M.P. Siesling S. Different statistical techniques dealing with confounding in observational research: measuring the effect of breast-conserving therapy and mastectomy on survival.J Cancer Res Clin Oncol. 2019; 145: 1485-1493Crossref PubMed Scopus (0) Google Scholar,9Guo S. Fraser M. Chen Q. Propensity score analysis: recent debate and discussion.J Soc Soc Work Res. 2020; 11: 463-482Crossref Scopus (63) Google Scholar Differences in outcomes between breast-conserving therapy and mastectomy after preoperative systemic therapy cannot be assessed by further randomized trials, due to ethical and practical reasons. Therefore, it is important to use available data from observational studies as well, while cautiously interpreting results as the risk of residual (unmeasured) confounding can never be eliminated. An important advantage of observational research is, moreover, that it is more reflective of the real-world population. Breast-conserving therapy has further advantages. It offers lower complication rates, shorter hospital stays, reduced need for pain medication and faster return to work and social life when compared with mastectomy. Importantly, it also avoids the need for breast reconstruction with its associated higher complication rates and high probability of additional symmetrizing and revisional procedures. If radiation therapy to the reconstructed breast is indicated, the risks of long-term complications and poorer cosmetic outcomes increase. Management strategies involving variation in timings, surgical methods, and treatment sequencing, are intensely debated without simple answers being available that would fit all individual patients and all clinical settings. The total burden on the individual patient (and in consequence, the health care system and society) is thus much lower when breast-conserving therapy can be offered, and the best strategy is, wherever possible, to avoid mastectomy and whole-breast reconstruction with its associated complexity.10de Boniface J. Szulkin R. Johansson A.L.V. Major surgical postoperative complications and survival in breast cancer: Swedish population-based register study in 57 152 women.Br J Surg. 2022; 109: 977-983Crossref PubMed Scopus (1) Google Scholar In the current era of shared decision-making with multiple treatment options, it is important to inform patients about all potential outcomes of therapy, including all these considerations. In conclusion, this work adds to the growing scientific evidence supporting the use of breast-conserving therapy as the preferred standard treatment for the vast majority of patients with early-stage breast cancer. The introduction of breast-conserving therapy was a seismic improvement in care when introduced some 3–4 decades ago. Extending the scope of breast-conserving therapy is one of the major advantages of preoperative systemic therapy, which we should fully exploit. All authors contributed equally to the writing of the manuscript. None of the authors have an conflict of interest related to this work. Maria-Joao Cardoso reported payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events Educational events from Novartis and from Lily, as well as Leadership or fiduciary role in other board, society, committee or advocacy group, paid or unpaid related to Mama Help President–Support Association for Breast Cancer Patients. Funding source: No funding was received related to this work. Long-term overall survival of patients who undergo breast-conserving therapy or mastectomy for early operable HER2-Positive breast cancer after preoperative systemic therapy: an observational cohort studyPeople with HER2-positive breast cancer who have already had PST are more likely to survive after BCT, especially if they get a pathological complete response in the axillary lymph nodes. These findings underscore the necessity for further investigation into how responses to PST can inform the choice of surgical intervention and the potential impact on overall survival. Such insights could lead to the development of innovative tools that support personalized surgical strategies in the management of breast cancer. Full-Text PDF Open Access