Omission of Breast Surgery in Exceptional Responders.

Breast cancer management has transformed significantly over the last decades, primarily through the integration of neoadjuvant systemic therapy (NST) and the evolving understanding of tumor biology, enabling more tailored treatment strategies. The aim of this review is to critically present the historical context and contemporary evidence surrounding the potential of omission of surgery post-NST, focusing on exceptional responders who have achieved a pathologic complete response (pCR). Identifying these exceptional responders before surgery remains a challenge, however standardized image-guided biopsy may allow optimized patient selection. The safety and feasibility of omitting breast and axillary surgeries in these exceptional responders are explored in ongoing clinical trials and the reported preliminary results appear promising. Moreover, understanding patient and physician perspectives regarding the potential elimination of surgery post-NST is integral. While some patients express a preference to omit or minimize surgery, the majority of healthcare providers are intrigued by the prospect of avoiding surgical interventions and endorse further research in this field.

De-escalation towards omission is the tipping point of individualizing breast cancer surgery.

Tailoring of breast cancer treatment to the individual has especially occurred in breast cancer surgery: paradigms have changed from Halsted's radical mastectomy in 1882, to simple mastectomy, to lumpectomy. Within the next decade, we might face another paradigm change of omitting breast cancer surgery at all in case of a complete response after neoadjuvant systemic treatment. In this article, we provide an overview of the reasoning for this new paradigm change, the criticism it has evoked, and under which conditions it might be incorporated into clinical practice. We also take a look at previous paradigm changes in breast cancer surgery and the insights they provide us in the current situation on a statistical but also on a psychological level.

Outcomes of Curative-Intent Treatment for Patients With Breast Cancer Presenting With Sternal or Mediastinal Involvement.

PURPOSE: Optimal treatment of patients diagnosed with de novo metastatic breast cancer limited to the mediastinum or sternum has never been delineated. Herein, we sought to determine the efficacy of multimodality treatment, including metastasis-directed radiation therapy, in curing patients with this presentation. METHODS AND MATERIALS: This is a single-institution retrospective cohort study of patients with de novo metastatic breast cancer treated from 2005 to 2014, with a 50-month median follow-up for the primary cohort. The primary patient cohort had metastasis limited to the mediastinum/sternum treated with curative intent (n = 35). We also included a cohort of patients with stage IIIC disease treated with curative intent (n = 244). Additional groups included a mediastinal/sternal palliative cohort (treatment did not include metastasis-directed radiation therapy; n = 14) and all other patients with de novo stage IV disease (palliative cohort; n = 1185). The primary study outcomes included locoregional recurrence-free survival (LRRFS), recurrence-free survival (RFS), and overall survival (OS), which were calculated using the Kaplan-Meier method. Cox multivariable models compared survival outcomes across treatment cohorts adjusted for molecular subtype, age, and race. RESULTS: For the mediastinal/sternal curative-intent cohort, 5-year LRRFS was 85%, RFS was 52%, and OS was 63%. After adjustment, there was no statistically significant difference in LRRFS (hazard ratio [HR], 0.39; 95% confidence interval [CI], 0.13-1.13; P = .08), RFS (HR, 0.87; 95% CI 0.50-1.49; P = .61), or OS (HR, 0.79; 95% CI 0.44-1.43; P = .44) between the stage IIIC cohort and the mediastinal/sternal curative-intent cohort (referent). In contrast, RFS was worse for the mediastinal/sternal palliative cohort (HR, 2.29; 95% CI 1.05-5.00; P = .04). OS was worst for the de novo stage IV palliative cohort (HR, 2.61; 95% CI 1.50-4.53; P < .001). CONCLUSIONS: For select patients presenting with breast cancer metastatic to the sternum and/or mediastinum, curative-intent treatment with chemotherapy, surgery, and radiation yields outcomes similar to those of stage IIIC disease and superior to de novo stage IV breast cancer treated with palliative intent.

Multimodality Imaging for Evaluating Response to Neoadjuvant Chemotherapy in Breast Cancer.

OBJECTIVE: Neoadjuvant chemotherapy is becoming the standard of care for patients with locally advanced breast cancer. Conventional imaging modalities used for the assessment of tumor response to neoadjuvant chemotherapy rely on changes in size or morphologic characteristics and, therefore, are inherently limited. CONCLUSION: Functional imaging technologies evaluate vascular, metabolic, biochemical, and molecular changes in cancer cells and have a unique ability to detect specific biologic tumor markers, assess therapeutic targets, predict early response to neoadjuvant chemotherapy, and guide individualized cancer therapy.

RTOG 9804: a prospective randomized trial for good-risk ductal carcinoma in situ comparing radiotherapy with observation.

PURPOSE: The Radiation Therapy Oncology Group 9804 study identified good-risk patients with ductal carcinoma in situ (DCIS), a breast cancer diagnosis found frequently in mammographically detected cancers, to test the benefit of radiotherapy (RT) after breast-conserving surgery compared with observation. PATIENTS AND METHODS: This prospective randomized trial (1998 to 2006) in women with mammographically detected low- or intermediate-grade DCIS, measuring less than 2.5 cm with margins ≥ 3 mm, compared RT with observation after surgery. The study was designed for 1,790 patients but was closed early because of lower than projected accrual. Six hundred thirty-six patients from the United States and Canada were entered; tamoxifen use (62%) was optional. Ipsilateral local failure (LF) was the primary end point; LF and contralateral failure were estimated using cumulative incidence, and overall and disease-free survival were estimated using the Kaplan-Meier method. RESULTS: Median follow-up time was 7.17 years (range, 0.01 to 11.33 years). Two LFs occurred in the RT arm, and 19 occurred in the observation arm. At 7 years, the LF rate was 0.9% (95% CI, 0.0% to 2.2%) in the RT arm versus 6.7% (95% CI, 3.2% to 9.6%) in the observation arm (hazard ratio, 0.11; 95% CI, 0.03 to 0.47; P < .001). Grade 1 to 2 acute toxicities occurred in 30% and 76% of patients in the observation and RT arms, respectively; grade 3 or 4 toxicities occurred in 4.0% and 4.2% of patients, respectively. Late RT toxicity was grade 1 in 30%, grade 2 in 4.6%, and grade 3 in 0.7% of patients. CONCLUSION: In this good-risk subset of patients with DCIS, with a median follow-up of 7 years, the LF rate was low with observation but was decreased significantly with the addition of RT. Longer follow-up is planned because the timeline for LF in this setting seems protracted.

Web based pathology assessment in RTOG 98-04.

AIMS: Radiation Therapy Oncology Group 98-04 sought to identify women with 'good risk' ductal carcinoma in situ (DCIS) who receive no significant benefit from radiation. Enrolment criteria excluded close or positive margins and grade 3 disease. To ensure reproducibility in identifying good risk pathology, an optional web based teaching tool was developed and a random sampling of 10% of submitted slides were reviewed by a central pathologist. METHODS: Submitting pathologists were asked to use the web based teaching tool and submit an assessment of the tool along with the pathology specimen form and DCIS H&E stained slide. Per protocol pathology was centrally reviewed for 10% of the cases. RESULTS: Of the 55 DCIS cases reviewed, three had close or positive margins and three were assessed to include grade 3 DCIS, therefore 95% of DCIS cases reviewed were correctly graded, and 89% reviewed were pathologically appropriate for enrolment. Regarding the teaching tool, 13% of DCIS cases included forms that indicated the website was used. One of these seven who used the website submitted DCIS of grade 3. CONCLUSIONS: Central review demonstrates high pathological concordance with enrolment eligibility, particularly with regard to accurate grading. The teaching tool appeared to be underused.