Surgery paradigm for locally advanced breast cancer following neoadjuvant systemic therapy.

Locally advanced breast cancer (LABC) remains a significant clinical challenge, particularly in developing countries. While neoadjuvant systemic therapy (NST) has improved the pathological complete response (pCR) rates, particularly in HER2-positive and triple-negative breast cancer patients, surgical management post-NST continues to evolve. The feasibility of omitting surgery and the increasing consideration of breast-conserving surgery, immediate reconstruction in LABC patients are important areas of exploration. Accurate assessment of tumor response to NST through advanced imaging and minimally invasive biopsies remains pivotal, though challenges persist in reliably predicting pCR. Additionally, axillary lymph node management continues to evolve, with emerging strategies aiming to minimize the extent of surgery in patients who achieve nodal downstaging post-NST. Minimizing axillary lymph node dissection in favor of less invasive approaches is gaining attention, though further evidence is needed to establish its oncological safety. The potential for personalized treatment approaches, reducing surgical morbidity, and improving quality of life are key goals in managing LABC, while maintaining the priority of achieving favorable long-term outcomes.

The efficacy of screening with FDG-PET/CT for distant metastases in breast cancer patients scheduled for neoadjuvant systemic therapy.

PURPOSE: This study aims to identify which breast cancer patients benefit from the routine use of FDG-PET/CT in a large cohort of patients scheduled for neoadjuvant systemic therapy (NST). METHODS: A total of 1337 breast cancer patients eligible for NST were identified from a retrospective database between 2011 and 2020 at a single tertiary care hospital. All patients underwent staging with FDG-PET/CT prior to NST. The incidence and extent of asymptomatic distant metastases in different patient subgroups were determined, as well as the impact on treatment. Logistic regression analysis was used to identify prognostic patient and tumor characteristics. RESULTS: FDG-PET/CT detected distant metastases in 109 patients (8%). Initial clinical stage was a prognostic factor for the presence of distant metastases, with a significantly higher risk for stage 2b and 3 as opposed to lower stages (p < 0.001). The incidence of distant metastases was 3% (4/125) for stage 1, 2% (8/534) for stage 2a, 7% (24/354) for stage 2b and 23% (73/324) for stage 3. Other characteristics such as age, tumor subtype, histological type and grade were not correlated with the risk of distant metastases. Among the subset of patients with distant metastases, 46% received palliative treatment, while the remaining 54% were diagnosed with oligometastatic breast cancer and were treated with curative intent. CONCLUSION: The results of the current study support the routine use of FDG-PET/CT for the detection of distant metastases in breast cancer patients with initial clinical stage 2b and 3, regardless of tumor subtype.

Developing machine learning models for personalized treatment strategies in early breast cancer patients undergoing neoadjuvant systemic therapy based on SEER database.

This study aimed to compare the long-term outcomes of breast-conserving surgery plus radiotherapy (BCS + RT) and mastectomy in early breast cancer (EBC) patients who received neoadjuvant systemic therapy (NST), and sought to construct and authenticate a machine learning algorithm that could assist healthcare professionals in formulating personalized treatment strategies for this patient population. We analyzed data from the Surveillance, Epidemiology, and End Results database on EBC patients undergoing BCS + RT or mastectomy post-NST (2010-2018). Employing propensity score matching (PSM) to minimize potential biases, we compared breast cancer-specific survival (BCSS) and overall survival (OS) between the two surgical groups. Additionally, we trained and validated six machine learning survival models and developed a cloud-based recommendation system for surgical treatment based on the optimal model. Among the 13,958 patients, 9028 (64.7%) underwent BCS + RT and 4930 (35.3%) underwent mastectomy. After PSM, there were 3715 patients in each group. Compared to mastectomy, BCS + RT significantly improved BCSS (p < 0.001) and OS (p < 0.001). Prognostic variables associated with BCSS were utilized to develop machine learning models. In both the training and validation cohorts, the random survival forest (RSF) model demonstrated superior predictive performance (0.847 and 0.795), not only outperforming other machine learning models, including Rpart (0.725 and 0.707), Xgboost (0.762 and 0.727), Glmboost (0.748 and 0.788), Survctree (0.764 and 0.766), and Survsvm (0.777 and 0.790), but also outperforming the classical COX model (0.749 and 0.782). Lastly, a web-based prediction tool was built to facilitate clinical application [ https://jhren.shinyapps.io/shinyapp1 ]. After adjusting other confounders, BCS + RT was associated with improved outcomes in patients with EBC after NST, compared to those who underwent mastectomy. Moreover, the RSF model, a reliable tool, can predict long-term outcomes for patients, providing valuable guidance for operative methods and postoperative follow-up.

Clinical Outcomes in Patients with Early Stage Node-Negative HER2-Positive Breast Cancer Receiving Upfront Surgery or Neoadjuvant Systemic Therapy.

BACKGROUND: HER2-positive breast cancer is traditionally treated with neoadjuvant systemic therapy (NST), but optimal treatment sequencing is less clear in patients with small tumors. We investigated clinicopathologic and oncologic outcomes in early stage HER2-positive breast cancer. PATIENTS AND METHODS: An institutional database was queried to identify patients with cT1-2 (≤ 3 cm) N0M0, HER2-positive breast cancer treated from 2015 to 2020 and compared upfront surgery and NST cohorts. Logistic regression was performed to identify factors predicting upstaging. Survival outcomes by group were compared using log-rank tests. RESULTS: Of 256 patients identified, 170 (66.4%) received upfront surgery and 86 (33.6%) NST. The NST cohort was younger and had more cT2 and grade 3 tumors and negative sentinel nodes. There was no significant difference in type of breast surgery or receipt of axillary lymphadenectomy. After upfront surgery, 4 (2.4%) patients had upstaging to pT > 3 cm and 18 (10.6%) to pN1-3. No factors predicted upstaging. After NST, 47 (54.7%) achieved pathologic complete response and 3 (3.5%) had upstaging to ypN1-3 with older age (OR 1.08, p = 0.004) and hormone receptor-positive status (OR 7.07, p = 0.002) identified as predictors. At median follow-up of 3.55 years, 10 (3.9%) patients had recurrence and 5 (2.0%) patients died. There were no significant differences in oncologic outcomes between groups. CONCLUSIONS: Patients with cT1-2 (≤ 3 cm)N0 HER2-positive breast cancer selected for NST have higher-risk disease. Low rates of pathologic upstaging were observed with no difference in surgical treatments and overall excellent oncologic outcomes in both groups. These findings may guide decision-making regarding treatment sequencing for patients with early stage HER2-positive disease.

Neoadjuvant Versus Adjuvant Systemic Therapy in Breast Cancer: A Matched Case-control Study.

BACKGROUND/AIM: Neoadjuvant systemic therapy (NAT) in breast cancer can make tumors resectable or reduce the extent of surgery needed for locally advanced cancers. It can also better prevent distant relapse and possibly modulate drug therapy by adjusting adjuvant therapy (AD) based on the response to NAT, either by escalating or de-escalating the treatment. However, clear evidence of improved outcomes is currently missing. Here, we report on breast cancer patients treated with NAT at our institution. PATIENTS AND METHODS: One hundred twenty-seven patients treated at our Radiation Oncology department between 2004 and 2021 were retrospectively analyzed. All patients had localized or locally advanced breast cancer, were treated with NAT, and received postoperative radiotherapy. The outcomes considered were overall survival (OS), loco-regional recurrence-free survival (LRRFS), and distant metastases-free survival (DMFS). A matched patient population treated with AD during the same period and at the same center was used for comparison. RESULTS: The 5-year predicted OS was 87% in the NAT group and 81.5% in the AD group (p-value=0.179), while LRRFS was 93.2% in the NAT group and 100% in the AD group (p=0.005). The 5-year predicted DMFS was 84.6% in the NAT group and 82.1% in AD patients (p=0.367). In the NAT group, the only prognostic factor significantly related to improved outcomes was the pathological node response, with an OS of 95.6% in patients without residual node disease compared to 75.1% in patients with evidence of residual node disease. CONCLUSION: Our study, despite the limitations of a small number of patients and its retrospective nature, confirms the data of previous larger studies. In terms of DMFS and OS, NAT is at least as effective as AD. NAT represents a great opportunity for personalized modulation of treatment in node-positive breast cancer patients.

Non-Invasive 3D Breast Tumor Localization: A Viable Alternative to Invasive Tumor Marking.

Background: We present a detailed description and the preliminary results of our original technique for non-invasive three-dimensional tumor localization in the breast, which was created as an alternative to standard invasive tumor marking before neoadjuvant systemic therapy (NAST), aiming to enable adequate surgery after complete tumor regression. Methods: A detailed description of the technique is provided in the main text. The technique's feasibility and precision were assessed in a single-arm, prospective study based on the histological parameters of the adequacy and rationality of the excision of completely regressed tumor beds. Results: Out of 94 recruited patients, 15 (16%) were deemed unsuitable, mainly due to the tumors' inadequate ultrasound visibility. Among the 79 processed patients, 31 (39%) had complete clinical regression after NAST and were operated on using our technique. The histological parameters of surgical precision (signs of tumor regression: 24/31; microscopic cancer residues: 7/31) were verified in all excised specimens (100% precision). There were no positive margins in seven cases with microscopic residues, indicating our technique's capacity to enable oncologically safe post-NAST surgery. Conclusions: The proposed technique is feasible and satisfactorily accurate in determining the location of regressed tumors, thus representing an alternative to invasive tumor marking, especially in surgical centers lacking trained staff and equipment for invasive marking. The technique's limitations are mainly related to the inadequate ultrasound visibility of the tumor.

Role of liver resection in the era of advanced systemic therapy for hepatocellular carcinoma.

The recent dramatic progress in systemic therapy for hepatocellular carcinoma (HCC) provides the possibility of a combination of surgery and systemic therapy including adjuvant, neoadjuvant, or conversion settings. Since the turn of the century, at least three negative studies have tested adjuvant therapies after curative resection or ablation, including uracil-tegafur, which is an oral chemotherapeutic drug, sorafenib, and peretinoin, which a synthetic retinoid that may induce the apoptosis and differentiation of liver cancer cells. Using more potent immuno-checkpoint inhibitors (ICIs), at least 4 phase III trials of adjuvant immunotherapy are ongoing: nivolumab, durvalumab/ bevacizumab, pembrolizumab, and atezolizumab+bevacizumab. Very recently, the last trial indicated a significantly better recurrence-free survival (RFS) for adjuvant atezolizumab+bevacizumab. Another promising combination of surgery and systemic therapy is neoadjuvant therapy for potentially resectable cases or a conversion strategy for oncologically unresectable cases. There are 2 neoadjuvant trials for technically or oncologically unresectable HCCs ongoing in Japan: the LENS-HCC trial using lenvatinib and the RACB study using atezolizumab+bevacizumab. A longer follow-up may be needed, but the overall survival (OS) in resected cases seems much higher than that in unresectable cases. Recently, the Japan Liver Cancer Association (JLCA) and the Japanese Society of HPB Surgery (JSHPBS) created a joint working group on "so-called borderline resectable HCC". They obtained a Japanese consensus on this issue that has been published on the websites of JLCA and JSHPBS. The definition of resectability or borderline resectability provides a common language regarding advanced HCC for investigators and is a useful tool for future clinical trials.

Use of neoadjuvant paclitaxel in breast angiosarcoma-Impact on surgical resection and response rates.

OBJECTIVE: Breast angiosarcoma is a tumor that can arise as a primary breast tumor or in association with prior radiation therapy. Angiosarcomas are uniquely sensitive to paclitaxel. This study evaluated the impact neoadjuvant paclitaxel (NAC) therapy has on surgical outcomes, tumor recurrence, and survival in breast angiosarcomas. METHODS: Patients with angiosarcoma of the breast, either primary or radiation-associated, were identified from a prospective institutional database. Patients receiving NAC were compared to those treated with upfront surgery. Clinical and pathological variables were compared using Student's t-test or Fisher's exact test, differences in survival were calculated using Kaplan-Meier methods. RESULTS: Twenty-four patients with angiosarcoma of the breast were identified, 10 with primary angiosarcoma and 14 with radiation-associated angiosarcoma. Twelve patients received NAC, 6 of each with primary angiosarcoma or radiation-associated angiosarcoma. Of these 12 patients, 11 had a margin negative resection (91%) of which, nine had a complete pathological response on surgical pathology. Of the 12 surgery-first patients, four (n = 4/12, 33%) had positive surgical margins, two of the four underwent reoperation. With a median follow-up of 16 months, four NAC patients had recurrence (33%) compared to six patients in the surgery-first group (58%) (p = 0.41). While not statistically significant, NAC patients had a 33% less risk of recurring compared to surgery-first patients ([hazard ratio =0.67 (95% confidence interval 0.16-2.72; p = 0.6]). CONCLUSION: NAC for breast angiosarcoma may be associated with high rates of complete pathological response and margin-negative resection. However, this did not impact overall survival. Future prospective control studies and longer follow-up periods are warranted to understand the impact on recurrence and survival.

Micrometastases in axillary lymph nodes in breast cancer, post-neoadjuvant systemic therapy.

INTRODUCTION: The significance of minimal residual axillary disease, specifically micrometastases, following neoadjuvant systemic therapy (NST) remains largely unexplored. Our study aimed to elucidate the prognostic implications of micrometastases in axillary and sentinel lymph nodes following NST. METHODS: This retrospective study analyzed primary breast cancer patients who underwent surgery after NST from September 2006 through February 2018. All patients received axillary lymph node dissection (ALND), either with or without sentinel lymph node biopsy. Recurrence-free survival (RFS)-associated variables were identified using a multivariate Cox proportional hazard model. RESULTS: Of the 978 patients examined, 438 (44.8%) exhibited no pathologic lymph node involvement (ypN0) after NST, while 89 (9.1%) had micrometastases (ypN1mi) and 451 (46.7%) had macrometastases (ypN+). Notably, 51.1% of the patients with sentinel lymph node micrometastases (SLNmi) had additional metastases, nearly triple that of SLN-negative patients (P < 0.001), and 29.8% of SLNmi patients were upstaged with the ALND. Although ypN1mi was not associated with RFS in patients post-NST (HR, 1.02; 95% CI, 0.42-2.49; P = 0.958), SLNmi patients experienced significantly worse RFS compared to SLN-negative patients (hazard ratio [HR], 2.23; 95% confidence intervals [CI], 1.12-4.46; P = 0.023). Additional metastases in SLNmi were more prevalent in patients with larger residual breast disease greater than 20 mm, HR-positive/HER2-negative subtype, and low Ki-67 LI (< 14%). CONCLUSIONS: SLNmi is a negative prognostic factor significantly associated with additional non-SLN metastases, while ypN1mi does not influence the prognosis compared to ypN0. Hence, additional ALND may be warranted to confirm axillary nodal status in patients with SLNmi.

Multiparametric MRI-based radiomic models for early prediction of response to neoadjuvant systemic therapy in triple-negative breast cancer.

Triple-negative breast cancer (TNBC) is often treated with neoadjuvant systemic therapy (NAST). We investigated if radiomic models based on multiparametric Magnetic Resonance Imaging (MRI) obtained early during NAST predict pathologic complete response (pCR). We included 163 patients with stage I-III TNBC with multiparametric MRI at baseline and after 2 (C2) and 4 cycles of NAST. Seventy-eight patients (48%) had pCR, and 85 (52%) had non-pCR. Thirty-six multivariate models combining radiomic features from dynamic contrast-enhanced MRI and diffusion-weighted imaging had an area under the receiver operating characteristics curve (AUC) > 0.7. The top-performing model combined 35 radiomic features of relative difference between C2 and baseline; had an AUC = 0.905 in the training and AUC = 0.802 in the testing set. There was high inter-reader agreement and very similar AUC values of the pCR prediction models for the 2 readers. Our data supports multiparametric MRI-based radiomic models for early prediction of NAST response in TNBC.

Reliability of Magseed® marking before neoadjuvant systemic therapy with subsequent contrast-enhanced mammography in patients with non-palpable breast cancer lesions after treatment: the MAGMA study.

PURPOSE: To assess the reliability of excising residual breast cancer lesions after neoadjuvant systemic therapy (NAST) using a previously localized paramagnetic seed (Magseed®) and the subsequent use of contrast-enhanced spectral mammography (CESM) to evaluate response. METHODS: Observational, prospective, multicenter study including adult women (> 18 years) with invasive breast carcinoma undergoing NAST between January 2022 and February 2023 with non-palpable tumor lesions at surgery. Radiologists marked tumors with Magseed® during biopsy before NAST, and surgeons excised tumors guided by the Sentimag® magnetometer. CESMs were performed before and after NAST to evaluate tumor response (Response Evaluation Criteria for Solid Tumors [RECIST]). We considered intraoperative, surgical, and CESM-related variables and histological response. RESULTS: We analyzed 109 patients (median [IQR] age of 55.0 [46.0, 65.0] years). Magseed® was retrieved from breast tumors in all surgeries (100%; 95% CI 95.47-100.0%) with no displacement and was identified by radiology in 106 patients (97.24%), a median (IQR) of 176.5 (150.0, 216.3) days after marking. Most surgeries (94.49%) were conservative; they lasted a median (IQR) of 22.5 (14.75, 40.0) min (95% CI 23.59-30.11 min). Most dissected tumor margins (93.57%) were negative, and few patients (5.51%) needed reintervention. Magseed® was identified using CESM in all patients (100%); RECIST responses correlated with histopathological evaluations of dissected tumors using the Miller-Payne response grade (p < 0.0001) and residual lesion diameter (p < 0.0001). Also 69 patients (63.3%) answered a patient's satisfaction survey and 98.8% of them felt very satisfied with the entire procedure. CONCLUSION: Long-term marking of breast cancer lesions with Magseed® is a reliable and feasible method in patients undergoing NAST and may be used with subsequent CESM.

Assessing the Efficacy of Radioactive Iodine Seed Localisation in Targeted Axillary Dissection for Node-Positive Early Breast Cancer Patients Undergoing Neoadjuvant Systemic Therapy: A Systematic Review and Pooled Analysis.

Targeted axillary dissection (TAD), employing marked lymph node biopsy (MLNB) alongside sentinel lymph node biopsy (SLNB), is increasingly recognised for its efficacy in reducing false negative rates (FNRs) in node-positive early breast cancer patients receiving neoadjuvant systemic therapy (NST). One such method, 125I radioactive seed localisation (RSL), involves implanting a seed into a biopsy-proven lymph node either pre- or post-NST. This systematic review and pooled analysis aimed to assess the performance of RSL in TAD among node-positive patients undergoing NST. Six studies, encompassing 574 TAD procedures, met the inclusion criteria. Results showed a 100% successful deployment rate, with a 97.6% successful localisation rate and a 99.8% retrieval rate. Additionally, there was a 60.0% concordance rate between SLNB and MLNB. The FNR of SLNB alone was significantly higher than it was for MLNB (18.8% versus 5.3%, respectively; p = 0.001). Pathological complete response (pCR) was observed in 44% of cases (248/564). On average, the interval from 125I seed deployment to surgery was 75.8 days (range: 0-272). These findings underscore the efficacy of RSL in TAD for node-positive patients undergoing NST, enabling precise axillary pCR identification and facilitating the safe omission of axillary lymph node dissection.

Phase 2 study of neoadjuvant enzalutamide and paclitaxel for luminal androgen receptor-enriched TNBC: Trial results and insights into "ARness".

Luminal androgen receptor (LAR)-enriched triple-negative breast cancer (TNBC) is a distinct subtype. The efficacy of AR inhibitors and the relevant biomarkers in neoadjuvant therapy (NAT) are yet to be determined. We tested the combination of the AR inhibitor enzalutamide (120 mg daily by mouth) and paclitaxel (80 mg/m2 weekly intravenously) (ZT) for 12 weeks as NAT for LAR-enriched TNBC. Eligibility criteria included a percentage of cells expressing nuclear AR by immunohistochemistry (iAR) of at least 10% and a reduction in sonographic volume of less than 70% after four cycles of doxorubicin and cyclophosphamide. Twenty-four patients were enrolled. Ten achieved a pathologic complete response or residual cancer burden-I. ZT was safe, with no unexpected side effects. An iAR of at least 70% had a positive predictive value of 0.92 and a negative predictive value of 0.97 in predicting LAR-enriched TNBC according to RNA-based assays. Our data support future trials of AR blockade in early-stage LAR-enriched TNBC.

Surgical outcomes and prognosis of HER2+ invasive breast cancer patients with a DCIS component treated with breast-conserving surgery after neoadjuvant systemic therapy.

INTRODUCTION: In up to 72 % of HER2+ invasive breast cancer (IBC), a ductal carcinoma in situ (DCIS) component is present. The presence of DCIS is associated with increased positive surgical margins after breast-conserving surgery (BCS). The aim of this study was to assess surgical margins, recurrence and survival in a nationwide cohort of HER2+ IBC with versus without a DCIS component, treated with neoadjuvant systemic therapy (NST) and BCS. MATERIALS AND METHODS: Women diagnosed with HER2+ IBC treated with NST and BCS, between 2010 and 2019, were selected from the Netherlands Cancer Registry and linked to the Dutch Nationwide Pathology Databank. Kaplan-Meier and Cox regression analyses were performed to determine locoregional recurrence rate (LRR) and overall survival (OS) and associated clinicopathological variables. Surgical outcomes and prognosis were compared between IBC only and IBC+DCIS. RESULTS: A total of 3056 patients were included: 1832 with IBC and 1224 with IBC+DCIS. Patients with IBC+DCIS had significantly more often positive surgical margins compared to IBC (12.8 % versus 4.9 %, p < 0.001). Five-year LRR was significantly higher in patients with IBC+DCIS compared to IBC (6.8 % versus 3.6 %, p < 0.001), but the presence of DCIS itself was not significantly associated with LRR after adjusting for confounders in multivariable analysis. Five-year OS did not differ between IBC+DCIS and IBC (94.9 % versus 95.7 %, p = 0.293). CONCLUSION: The presence of DCIS is associated with higher rates of positive surgical margins, but not with LRR and lower OS when adjusted for confounders. Further research is necessary to adequately select IBC+DCIS patients for BCS after NST.

Evaluating Magnetic Seed Localization in Targeted Axillary Dissection for Node-Positive Early Breast Cancer Patients Receiving Neoadjuvant Systemic Therapy: A Comprehensive Review and Pooled Analysis.

Background/Objectives: De-escalation of axillary surgery is made possible by advancements in both neoadjuvant systemic therapy (NST) and in localisation technology for breast lesions. Magseed®, developed in 2013 by Dr. Michael Douk of Cambridge, United Kingdom, is a wire-free localisation technology that facilitates the localisation and retrieval of lymph nodes for staging. Targeted axillary dissection (TAD), which entails marked lymph node biopsy (MLNB) and sentinel lymph node biopsy (SLNB), has emerged as the preferred method to assess residual disease in post-NST node-positive patients. This systematic review and pooled analysis evaluate the performance of Magseed® in TAD. Methods: The search was carried out in PubMed and Google Scholar. An assessment of localisation, retrieval rates, concordance between MLNB and SLNB, and pathological complete response (pCR) in clinically node-positive patients post NST was undertaken. Results: Nine studies spanning 494 patients and 497 procedures were identified, with a 100% successful deployment rate, a 94.2% (468/497) [95% confidence interval (CI), 93.7-94.7] localisation rate, a 98.8% (491/497) retrieval rate, and a 68.8% (247/359) [95% CI 65.6-72.0] concordance rate. pCR was observed in 47.9% (220/459) ) [95% CI 43.3-52.6] of cases. Subgroup analysis of studies reporting the pathological status of MLNB and SLNB separately revealed an FNR of 4.2% for MLNB and 17.6% for SLNB (p = 0.0013). Mean duration of implantation was 37 days (range: 0-188). Conclusions: These findings highlight magnetic seed localisation's efficacy in TAD for NST-treated node-positive patients, aiding in accurate axillary pCR identification and safe de-escalation of axillary surgery in excellent responders.

Axillary Management: How Much Is Too Much?

PURPOSE OF REVIEW: To review the current management of the axilla in breast cancer. RECENT FINDINGS: Axillary dissection is no longer indicated in patients with clinically node-negative axilla with 1-2 positive sentinel lymph nodes following upfront surgery or in patients with clinically node-negative axilla following neoadjuvant chemotherapy. Breast cancer has evolved away from routine axillary clearance to the less invasive sentinel lymph node biopsy to now complete omission of axillary sampling in select patients. We will review the most salient evidence that has shaped these practice changes over the last three decades. Current practice controversies are especially relevant for elderly populations and those receiving neoadjuvant therapy. Ongoing clinical trials will provide data to further guide breast cancer surgical management.

Systemic Therapy Advances for HER2-Positive and Triple Negative Breast Cancer: What the Surgeon Needs to Know.

Neoadjuvant systemic therapy (NST) was initially reserved for unresectable patients however it has been increasingly used to facilitate breast conservation, downstage the axilla, and inform adjuvant therapy decisions based on response. For patients with HER2+ and triple-negative breast cancer (TNBC), clinical trials have resulted in the ability to individualize treatment regimens. For HER2+ breast cancer, de-escalation of neoadjuvant regimens to minimize cytotoxic chemotherapy and de-escalation or escalation of adjuvant regimens based on response have been effective. For TNBC, the approval of the combination of chemotherapy plus immunotherapy in the neoadjuvant setting has resulted in a major practice shift and opened the door to many additional treatment questions including de-escalation of the chemotherapy backbone or the adjuvant regimen. For both HER2+ and TNBC, most patients are treated with NST except those with very small tumors. Efforts are also being made to optimally identify patients with T1c tumors who may benefit from more aggressive NST. For patients treated according to or enrolled in NST de-escalation trials, breast conservation (even those who become eligible based on response to NST) and sentinel lymph node biopsy when cN0 at the completion of NST are safe and feasible. Continued involvement of surgeons and multidisciplinary teams in the design and reporting of trials will streamline their adoption into clinical practice. Surgeons need to remain aware of ongoing systemic therapy trials to appropriately select patients for NST and plan for appropriate post-neoadjuvant surgical care.

Can neoadjuvant systemic therapy provide additional benefits for T1 HER2+ breast cancer patients: a subgroup analysis based on different high-risk signatures.

INTRODUCTION: Neoadjuvant systemic therapy (NAST) is vital in the management of HER2-positive (HER2+) breast cancer. Nevertheless, the indications for NAST in tumors <2 cm remain controversial. METHOD: A total of 7961 patients were screened from the Surveillance, Epidemiology, and End Result database. Independent prognostic factors were identified using multivariate Cox analysis. Subgroup analyses and Kaplan-Meier analyses were used to simulate whether NAST would provide a survival benefit with different high-risk characteristics. Nomograms were constructed, and an internal validation cohort was employed. RESULTS: Of the 7961 included patients, 1137 (14.3%) underwent NAST. In the total population, NAST was associated with poorer overall survival (OS) and breast cancer-specific survival (BCSS) (OS: P = 0.00093; BCSS: P  <  0.0001). Multivariate Cox analysis confirmed that NAST markedly affected the prognosis of enrolled patients. Besides, a direct association between T, N, age, subtype, and prognosis was observed. Subgroup analyses yielded in these three subgroups, T1c, hormone receptor-negative, and 61-69 years of age, NAST and AST had comparable OS, while NAST possessed worse BCSS. Notably, even in the N3, we still did not observe any additional benefit of NAST. The calculated C-index of 0.72 and 0.73 confirmed the predictability of the nomograms. The AUCs exhibit consistency in the training and validation cohorts. CONCLUSION: Our findings suggest that NAST does not provide additional benefit to patients with T1 HER2+ breast cancer, even in the presence of lymph node metastasis, T1c, or hormone receptor negativity. This study facilitates the implementation of individualized management strategies.

Determining individual suitability for neoadjuvant systemic therapy in breast cancer patients through deep learning.

BACKGROUND: The survival advantage of neoadjuvant systemic therapy (NST) for breast cancer patients remains controversial, especially when considering the heterogeneous characteristics of individual patients. OBJECTIVE: To discern the variability in responses to breast cancer treatment at the individual level and propose personalized treatment recommendations utilizing deep learning (DL). METHODS: Six models were developed to offer individualized treatment suggestions. Outcomes for patients whose actual treatments aligned with model recommendations were compared to those whose did not. The influence of certain baseline features of patients on NST selection was visualized and quantified by multivariate logistic regression and Poisson regression analyses. RESULTS: Our study included 94,487 female breast cancer patients. The Balanced Individual Treatment Effect for Survival data (BITES) model outperformed other models in performance, showing a statistically significant protective effect with inverse probability treatment weighting (IPTW)-adjusted baseline features [IPTW-adjusted hazard ratio: 0.51, 95% confidence interval (CI), 0.41-0.64; IPTW-adjusted risk difference: 21.46, 95% CI 18.90-24.01; IPTW-adjusted difference in restricted mean survival time: 21.51, 95% CI 19.37-23.80]. Adherence to BITES recommendations is associated with reduced breast cancer mortality and fewer adverse effects. BITES suggests that patients with TNM stage IIB, IIIB, triple-negative subtype, a higher number of positive axillary lymph nodes, and larger tumors are most likely to benefit from NST. CONCLUSIONS: Our results demonstrated the potential of BITES to aid in clinical treatment decisions and offer quantitative treatment insights. In our further research, these models should be validated in clinical settings and additional patient features as well as outcome measures should be studied in depth.