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Simple Summary: The management of the axilla for post-mastectomy breast cancer patients who develop a chest wall recurrence (CWR) remains to be established. This study aimed to determine if omitting axillary staging surgery for these patients resulted in an increased risk of second recurrence. A total of 194 patients with CWR, with a median follow-up of 59.5 (IQR 27.3–105) months, were analysed. There was no statistically significant difference in second recurrences between patients with or without axillary surgery during the excision of the CWR. Background: The management of the axilla in breast cancer patients with isolated chest wall recurrence (CWR) after mastectomy remains controversial. Although sentinel lymph node biopsy (SLNB) for restaging is feasible, its role is unclear. We aimed to determine if the omission of axillary restaging surgery in female patients with operable presumably isolated CWRs could result in an increased risk of second recurrences. Methods: In this retrospective multicentre study, patients who developed CWRs were reviewed. We excluded patients with suspected or concomitant regional/distant metastases, bilateral cancers and patients without CWR surgery. Patients' demographics, pathological data and subsequent recurrences were collected from a prospective database and were compared between patients with axillary lymph node dissection (ALND) and/or SLNB versus no axillary operation at CWR. Findings: A total of 194 patients with CWRs were eligible. The median age at CWR was 56.0 (IQR 47.0–67.0) years old. At recurrence, 8 (4.1%), 5 (2.6%) and 181 (93.3%) patients had ALND, SLNB and no axillary operation, respectively. Patients with no axillary surgery during CWR were associated with, at primary cancer, a lower incidence of ductal carcinoma in situ as diagnosis (p = 0.007) and older age (p = 0.022). Subsequent ipsilateral axillary (p = 0.768) and second recurrences (p = 0.061) were not statistically different between patients with and without axillary surgery at CWR on median follow-up of 59.5 (IQR 27.3–105) months. Interpretation: In patients without evidence of concomitant regional or distant metastasis at CWR diagnosis, omission of axillary restaging surgery was not associated with an increased ipsilateral axillary or second recurrences on long-term follow-up. [ABSTRACT FROM AUTHOR]

Simple Summary: In the last few decades, studies have found many common genetic variants linked to breast cancer. Most of these variants are in non-coding regions or regions that do not directly affect gene function. This study aims to see if a polygenic risk score (PRS) based on functional variants could better predict breast cancer risk compared to an established 313-variant breast cancer PRS. Using publicly available summary data from GWASs, and Quantitative Trait Locus studies of gene expression and DNA methylation, we identified 149 variants potentially causally linked to the risk of developing breast cancer; the weighted sum of these variants was designated as the functional variant. The functional PRS was less effective at predicting breast cancer than the established PRS in 3560 breast cancer patients and 3383 non-breast cancer individuals. Combining both scores did not substantially enhance the prediction accuracy of the established PRS. Purpose: To assess the association of a polygenic risk score (PRS) for functional genetic variants with the risk of developing breast cancer. Methods: Summary data-based Mendelian randomization (SMR) and heterogeneity in dependent instruments (HEIDI) were used to identify breast cancer risk variants associated with gene expression and DNA methylation levels. A new SMR-based PRS was computed from the identified variants (functional PRS) and compared to an established 313-variant breast cancer PRS (GWAS PRS). The two scores were evaluated in 3560 breast cancer cases and 3383 non-cancer controls and also in a prospective study (n = 10,213) comprising 418 cases. Results: We identified 149 variants showing pleiotropic association with breast cancer risk (eQTLHEIDI > 0.05 = 9, mQTLHEIDI > 0.05 = 165). The discriminatory ability of the functional PRS (AUCcontinuous [95% CI]: 0.540 [0.526 to 0.553]) was found to be lower than that of the GWAS PRS (AUCcontinuous [95% CI]: 0.609 [0.596 to 0.622]). Even when utilizing 457 distinct variants from both the functional and GWAS PRS, the combined discriminatory performance remained below that of the GWAS PRS (AUCcontinuous, combined [95% CI]: 0.561 [0.548 to 0.575]). A binary high/low-risk classification based on the 80th centile PRS in controls revealed a 6% increase in cases using the GWAS PRS compared to the functional PRS. The functional PRS identified an additional 12% of high-risk cases but also led to a 13% increase in high-risk classification among controls. Similar findings were observed in the SCHS prospective cohort, where the GWAS PRS outperformed the functional PRS, and the highest-performing PRS, a combined model, did not significantly improve over the GWAS PRS. Conclusions: While this study identified potentially functional variants associated with breast cancer risk, their inclusion did not substantially enhance the predictive accuracy of the GWAS PRS. [ABSTRACT FROM AUTHOR]

Simple Summary: Synchronous bilateral breast cancers are uncommon. While metastatic staging guidelines in patients with unilateral cancer are established, the indication for metastatic staging in patients with bilateral breast cancers remains unclear. This study aimed to retrospectively determine if all synchronous bilateral breast cancer patients need metastatic staging at diagnosis. This is the first such reported study, to the best of our knowledge. In our study, negative nodal status was predictive for negative metastatic staging results at diagnosis in patients with synchronous bilateral breast cancers. Nodal status alone, however, may not detect all cases with systemic metastasis. Hence, symptoms of systemic metastasis and metastatic nodal status could be used to determine the subgroup of synchronous bilateral invasive cancer patients who require metastatic staging. This finding could be validated in larger studies. Background: Patients with bilateral breast cancers are uncommon and are associated with a poorer prognosis. While metastatic staging guidelines in patients with unilateral cancer were established, the indication of metastatic staging in patients with bilateral breast cancers is unclear. We aimed to determine which patients with synchronous bilateral breast cancers require metastatic staging at diagnosis. This is the first such reported study, to the best of our knowledge. Methods: A retrospective review of newly diagnosed synchronous bilateral invasive breast cancer patients at our institution was performed. We excluded patients with malignant phyllodes or no metastatic staging. Patients' demographics and pathological and staging results were analysed to determine the group of bilateral breast cancer patients who required metastatic staging. Results: A total of 92 patients with synchronous bilateral invasive cancers were included. The mean age was 58 years old, and 64.1% had bilateral invasive ductal carcinoma. 23.9% had systemic metastasis. Nodal status was statistically significant for systemic metastasis on staging (p = 0.0081), with only three patients (3.3%) having negative nodal status and positive metastatic staging. These three patients, however, showed symptoms of distant metastasis. 92.3% of patients with negative nodes also had negative metastatic staging. Using negative nodal status as a guide avoided metastatic staging in 40.4% of all patients. Conclusions: Negative nodal status was the most predictive factor for no systemic metastasis on staging in patients with synchronous bilateral invasive breast cancers. Hence, metastatic staging could be reserved for patients with symptoms of systemic metastasis and/or metastatic nodes. This finding could be validated in larger studies. [ABSTRACT FROM AUTHOR]

INTRODUCTION: Ductal carcinoma in situ (DCIS) in young women is rare and not well studied. Since they do not qualify for mammographic screening, they are more likely to present with symptoms. Young women have also been associated with poorer outcomes, but it is unknown whether presentation mode affects outcome. We aimed to compare characteristics of DCIS patients <40 years of age presenting with symptoms versus those without, and determine whether presentation mode affects recurrence. METHODS: Pure DCIS patients aged <40 years were retrospectively analyzed. Clinical presentation, pathology and recurrence data were collected. Statistical analysis was performed to investigate the correlation of presentation mode with outcomes. RESULTS: 40 patients with 41 cases were included. The mean age at diagnosis was 32.3 years (range 17–39). 73.2% and 26.8% presented with symptoms or abnormal imaging respectively. Of the cases who presented with symptoms, 86.7%, 10.0% and 3.3% had palpable lump, nipple discharge or breast pain, respectively. The average tumor size was 22.0 mm (range 2.0–86.9) and 12.2 mm (range 3–25) for patients who presented with symptoms and non-symptomatic group, respectively. Cases presenting with symptoms were statistically associated with higher grade (p = 0.0090). On median follow-up of 85 months, there were 3 (7.3%) recurrences, which were not statistically associated with presentation mode. CONCLUSION: Young women with DCIS tend to present with symptoms, with breast lump as the commonest symptom. Symptomatic patients tend to be associated with grade III tumours, compared to non-symptomatic patients. On long-term follow-up, mode of presentation was not statistically associated with recurrence. [ABSTRACT FROM AUTHOR]

Introduction: Oncoplastic breast-conserving surgery (OBCS) can cause breast asymmetry. Although contralateral breast surgery to achieve symmetry was offered to these patients, the uptake of symmetrisation was variable. We aimed to determine the factors that deter patients with breast cancer undergoing OBCS from opting for symmetrisation.Methods: All patients with breast cancer who underwent OBCS of displacement type with no symmetrisation were prospectively surveyed to explore the social, economic, psychological and physical reasons against symmetrisation.Results: A total of 28 patients participated in a survey administered at a mean 21.6 (range 2-47) months after OBCS. A combination of factors, such as worry and desire to treat breast cancer first (67.9%), not being overly concerned about breast cosmesis (57.1%) and fear of pain from additional operation (28.6%), deterred patients from immediate symmetrisation. Worry and desire to treat breast cancer first was the most important single factor for 50% of the patients. Reasons for no delayed symmetrisation included not being overly concerned about breast cosmesis (70.4%), fear of breast cancer recurrence (48.1%) and being happy with current breast cosmesis (33.3%), with the former two reasons equally cited as the single most important deterrent by 30% of patients each.Conclusion: A combination of factors may deter patients from symmetrisation. The most significant factors deterring OBCS among patients were worry and desire to treat breast cancer first for immediate symmetrisation, and not being overly concerned about breast cosmesis and fear of breast cancer recurrence for delayed symmetrisation. Reassuring these patients may increase their uptake of symmetrisation, thereby improving patient cosmesis and satisfaction. [ABSTRACT FROM AUTHOR]

Purpose: Neoadjuvant chemotherapy (NAC) is increasingly used in breast cancer. Predictive modeling is useful in predicting pathologic complete response (pCR) to NAC. We test machine learning (ML) models to predict pCR in breast cancer and explore methods of handling missing data., Methods: Four hundred and ninety-nine patients with breast cancer treated with NAC in two centers in Singapore (National Cancer Centre Singapore [NCCS] and KK Hospital) between January 2014 and December 2017 were included. Eleven clinical features were used to train five different ML models. Listwise deletion and imputation were evaluated on handling missing data. Model performance was evaluated by AUC and calibration (Brier score). Feature importance from the best performing model in the external testing data set was calculated using Shapley additive explanations., Results: Seventy-two (24.6%), 18 (24.7%), and 31 (24.8%) patients attained pCR in NCCS training, NCCS testing, and KK Women's and Children's Hospital (KKH) testing data sets, respectively. The random forest (RF) base and imputed models have the highest AUCs in the KKH cohort of 0.794 (95% CI, 0.709 to 0.873) and 0.795 (95% CI, 0.706 to 0.871), respectively, and were the best calibrated with the lowest Brier score. No statistically significant difference was noted between AUCs of the base and imputed models in all data sets. The imputed model had a larger positive predictive value (PPV; 98.2% v 95.1%) and negative predictive value (NPV; 96.7% v 90.0%) than the base model in the KKH data set. Estrogen receptor intensity, human epidermal growth factor 2 intensity, and age at diagnosis were the three most important predictors., Conclusion: ML, particularly RF, demonstrates reasonable accuracy in pCR prediction after NAC. Imputing missing fields in the data can improve the PPV and NPV of the pCR prediction model.

Clinical genetic testing identifies variants causal for hereditary cancer, information that is used for risk assessment and clinical management. Unfortunately, some variants identified are of uncertain clinical significance (VUS), complicating patient management. Case-control data is one evidence type used to classify VUS, and previous findings indicate that case-control likelihood ratios (LRs) outperform odds ratios for variant classification. As an initiative of the Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA) Analytical Working Group we analyzed germline sequencing data of BRCA1 and BRCA2 from 96,691 female breast cancer cases and 303,925 unaffected controls from three studies: the BRIDGES study of the Breast Cancer Association Consortium, the Cancer Risk Estimates Related to Susceptibility consortium, and the UK Biobank. We observed 11,227 BRCA1 and BRCA2 variants, with 6,921 being coding, covering 23.4% of BRCA1 and BRCA2 VUS in ClinVar and 19.2% of ClinVar curated (likely) benign or pathogenic variants. Case-control LR evidence was highly consistent with ClinVar assertions for (likely) benign or pathogenic variants; exhibiting 99.1% sensitivity and 95.4% specificity for BRCA1 and 92.2% sensitivity and 86.6% specificity for BRCA2 . This approach provides case-control evidence for 785 unclassified variants, that can serve as a valuable element for clinical classification.

Background: In postoperative setting, breast cancer (BC) patients can experience adverse effects, including fatigue, sleep disorders, and pain, which substantially affect their health-related quality of life (HRQoL). This study sought to assess the effectiveness of a WeChat-based multimodal nursing program (WCBMNP) that was specifically designed for the rehabilitation of women following BC surgery., Methods: BC patients were randomly, single-blinded allocated to either the intervention (n=62) or control (n=63) cohorts. Over a period of 6 months (24 weeks), the intervention cohort received a WCBMNP in addition to routine nursing care, while the control cohort received routine nursing care only. To evaluate patients' fear of cancer recurrence (FCR), their overall fear score was assessed using the Japanese version of the Concerns About Recurrence Scale (CARS-J) for primary outcome. The initial outcome (HRQoL) and secondary results, such as fatigue, sleep, and pain, were examined using the Functional Assessment of Cancer Therapy-Breast (FACT-B, version 4.0) and Nursing Rating Scale (NRS), respectively., Results: Two hundred and ten participants, 85 participants were excluded. Compared to the controls (n=63), the intervention cohort (n=62) showed statistically significant improvements in their CARS-J scores. The intervention cohort aggregate scores on the FACT-B improved significantly but were affected by the compounding influences of cohort dynamics, temporal progression, and their interaction. Similar improvements were observed in the social/family and functional well-being domains. Emotional well-being was improved based on the effects of time and group-time interaction. In the intervention cohort, the "BC-specific subscale for additional concerns" was affected by group and time, whereas physical well-being was only affected by time. Conversely, there were no statistically significant changes in the variables of fatigue, sleep, and pain., Conclusions: The WCBMNP reduced FCR and significantly increased the HRQoL of female patients with BC postoperatively. The WCBMNP could be implemented as a postoperative rehabilitation intervention in this patient population to improve outcomes., Trial Registration: Chinese Clinical Trial Registry (ChiCTR2400081557)., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://gs.amegroups.com/article/view/10.21037/gs-24-40/coif). The authors have no conflicts of interest to declare., (2024 Gland Surgery. All rights reserved.)

Background: Patients with bilateral breast cancers are uncommon and are associated with a poorer prognosis. While metastatic staging guidelines in patients with unilateral cancer were established, the indication of metastatic staging in patients with bilateral breast cancers is unclear. We aimed to determine which patients with synchronous bilateral breast cancers require metastatic staging at diagnosis. This is the first such reported study, to the best of our knowledge., Methods: A retrospective review of newly diagnosed synchronous bilateral invasive breast cancer patients at our institution was performed. We excluded patients with malignant phyllodes or no metastatic staging. Patients' demographics and pathological and staging results were analysed to determine the group of bilateral breast cancer patients who required metastatic staging., Results: A total of 92 patients with synchronous bilateral invasive cancers were included. The mean age was 58 years old, and 64.1% had bilateral invasive ductal carcinoma. 23.9% had systemic metastasis. Nodal status was statistically significant for systemic metastasis on staging ( p = 0.0081), with only three patients (3.3%) having negative nodal status and positive metastatic staging. These three patients, however, showed symptoms of distant metastasis. 92.3% of patients with negative nodes also had negative metastatic staging. Using negative nodal status as a guide avoided metastatic staging in 40.4% of all patients., Conclusions: Negative nodal status was the most predictive factor for no systemic metastasis on staging in patients with synchronous bilateral invasive breast cancers. Hence, metastatic staging could be reserved for patients with symptoms of systemic metastasis and/or metastatic nodes. This finding could be validated in larger studies.

Background: In breast cancer patients fulfilling the Z0011 trial criteria, axillary lymph node dissection (ALND) is reserved for patients with a high nodal burden of ≥3 metastatic nodes. In this group of patients, to avoid an ALND, neoadjuvant chemotherapy (NACT) could be given instead to achieve nodal pathological complete response (pCR). However, the benefit of NACT in achieving nodal pCR and avoiding ALND in this group of patients is unknown. We aimed to determine the nodal pCR rate in this group of patients who otherwise would have needed an ALND., Methods: cT1-2N0 breast cancer patients, with histologically proven nodal metastasis, who underwent NACT were identified from a prospectively maintained database. The sonographic criteria of ≥3 abnormal nodes, which has been reported as highly predictive of high nodal burden, was then used to identify the high nodal burden group. Nodal pCR was determined based on the ALND following NACT., Results: Twenty-four patients with high nodal burden were identified. Mean age was 55.2 years. 91.7% had invasive ductal carcinoma and 29.2% had grade III cancer. 54.2% achieved nodal pCR which was associated with ypT (P=0.006). Nodal pCR was 75%, 70% and 30% in the triple negative, human epidermal growth factor receptor2 (HER2) positive and ER/PR+HER2- tumors, respectively., Conclusions: In the postulated T1-2 breast cancer patients with high nodal burden, needing an upfront ALND, NACT could result in nodal pCR of 54.2%, with higher pCR in certain subtypes. Hence, to minimize ALND risk, NACT should be offered in this high nodal burden group., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://gs.amegroups.com/article/view/10.21037/gs-22-7/coif). The authors have no conflicts of interest to declare., (2022 Gland Surgery. All rights reserved.)

Introduction: Oncoplastic breast-conserving surgery (OBCS) can cause breast asymmetry. Although contralateral breast surgery to achieve symmetry was offered to these patients, the uptake of symmetrisation was variable. We aimed to determine the factors that deter patients with breast cancer undergoing OBCS from opting for symmetrisation., Methods: All patients with breast cancer who underwent OBCS of displacement type with no symmetrisation were prospectively surveyed to explore the social, economic, psychological and physical reasons against symmetrisation., Results: A total of 28 patients participated in a survey administered at a mean 21.6 (range 2-47) months after OBCS. A combination of factors, such as worry and desire to treat breast cancer first (67.9%), not being overly concerned about breast cosmesis (57.1%) and fear of pain from additional operation (28.6%), deterred patients from immediate symmetrisation. Worry and desire to treat breast cancer first was the most important single factor for 50% of the patients. Reasons for no delayed symmetrisation included not being overly concerned about breast cosmesis (70.4%), fear of breast cancer recurrence (48.1%) and being happy with current breast cosmesis (33.3%), with the former two reasons equally cited as the single most important deterrent by 30% of patients each., Conclusion: A combination of factors may deter patients from symmetrisation. The most significant factors deterring OBCS among patients were worry and desire to treat breast cancer first for immediate symmetrisation, and not being overly concerned about breast cosmesis and fear of breast cancer recurrence for delayed symmetrisation. Reassuring these patients may increase their uptake of symmetrisation, thereby improving patient cosmesis and satisfaction., (Copyright: © Singapore Medical Association.)