Contralateral Breast Cancer Research Articles

Volumetric Breast Density Estimation From Three-Dimensional Reconstructed Digital Breast Tomosynthesis Images Using Deep Learning.

Breast density is a widely established independent breast cancer risk factor. With the increasing utilization of digital breast tomosynthesis (DBT) in breast cancer screening, there is an opportunity to estimate volumetric breast density (VBD) routinely. However, current available methods extrapolate VBD from two-dimensional (2D) images acquired using DBT and/or depend on the existence of raw DBT data, which is rarely archived by clinical centers because of storage constraints. We retrospectively analyzed 1,080 nonactionable three-dimensional (3D) reconstructed DBT screening examinations acquired between 2011 and 2016. Reference tissue segmentations were generated using previously validated software that uses 3D reconstructed slices and raw 2D DBT data. We developed a deep learning (DL) model that segments dense and fatty breast tissue from background. We then applied this model to estimate %VBD and absolute dense volume (ADV) in cm3 in a separate case-control sample (180 cases and 654 controls). We created two conditional logistic regression models, relating each model-derived density measurement to likelihood of contralateral breast cancer diagnosis, adjusted for age, BMI, family history, and menopausal status. The DL model achieved unweighted and weighted Dice scores of 0.88 (standard deviation [SD] = 0.08) and 0.76 (SD = 0.15), respectively, on the held-out test set, demonstrating good agreement between the model and 3D reference segmentations. There was a significant association between the odds of breast cancer diagnosis and model-derived VBD (odds ratio [OR], 1.41 [95 % CI, 1.13 to 1.77]; P = .002), with an AUC of 0.65 (95% CI, 0.60 to 0.69). ADV was also significantly associated with breast cancer diagnosis (OR, 1.45 [95% CI, 1.22 to 1.73]; P < .001) with an AUC of 0.67 (95% CI, 0.62 to 0.71). DL-derived density measures derived from 3D reconstructed DBT images are associated with breast cancer diagnosis.

Secondary Risk-Reducing Strategies for Contralateral Breast Cancer in BRCA1/2 Variant Carriers: A Systematic Review and Meta-analysis.

Breast cancer poses significant challenges, especially the increased risk of contralateral breast cancer (CBC) in BRCA1/2 variant carriers. This study systematically reviews and analyzes the effectiveness of secondary risk-reducing strategies for CBC in BRCA1/2 carriers. A systematic review and meta-analysis were conducted from January 2000 to December 2023, including RCTs, cohort, or case-control studies involving BRCA carriers with unilateral breast cancer. Random-effects models were used for odds ratios (ORs) on CBC incidence and hazard ratios (HRs) for overall survival (OS), with bias assessed via the Newcastle-Ottawa Scale. A total of 23,840 participants from 26 studies were included. Secondary risk-reducing interventions reduced CBC incidence by 38% [OR 0.62, 95% confidence interval (CI) 0.57-0.68] and improved OS by 45% (HR 0.55, 95% CI 0.46-0.67). Subgroup analyses showed differences by BRCA type, menopausal status, and treatment duration. For BRCA1 carriers, chemotherapy was most effective, while, for BRCA2, it was endocrine therapy. Postmenopausal interventions reduced CBC by 47% (OR 0.53, 95% CI 0.40-0.71), while premenopausal carriers saw a 34% reduction (OR 0.66, 95% CI 0.53-0.82). Tamoxifen's effect diminished over time. Secondary prophylaxis reduces CBC and improves OS in BRCA1/2 carriers, with variations by genetic and physiological factors. These findings underscore the need for personalized strategies, considering menopausal status and treatment duration.

Pathogenic variants in cancer susceptibility genes predispose to Ductal Carcinoma In situ of the breast.

To determine the relationship between germline pathogenic variants (PVs) in cancer predisposition genes and the risk of ductal carcinoma in situ (DCIS). Germline PV frequencies in breast cancer predisposition genes (ATM, BARD1, BRCA1, BRCA2, CDH1, CHEK2, PALB2, RAD51C, and RAD51D) were compared between DCIS cases and unaffected controls, and between DCIS and infiltrating ductal carcinoma (IDC) cases from a clinical-testing cohort (n=9,887), a population-based cohort (n=3,876) and the UK Biobank (n=2421). The risk of contralateral breast cancer for DCIS cases with PVs was estimated in the population-based cohort. Germline PVs were observed in 6.5% and 4.6% of women with DCIS in the clinical-testing and population-based cohorts, respectively. BRCA1, BRCA2, and PALB2 PVs frequencies were significantly lower among women with DCIS than IDC (clinical cohort: 2.8% vs. 5.7%; population-based cohort: 1.7% vs. 3.7%), whereas the PV frequencies for ATM and CHEK2 were similar. ATM, BRCA1, BRCA2, CHEK2, and PALB2 PVs were significantly associated with an increased risk of DCIS (OR>2.0), but only BRCA2 PVs were associated with high-risk (OR>4) in both cohorts. The cumulative incidence of contralateral breast cancer among carriers of PVs in high penetrance genes with DCIS was 23% over 15 years. The enrichment of PVs in ATM, BRCA1, BRCA2, CHEK2 and PALB2 among women with DCIS suggests that multigene panel testing may be appropriate for women with DCIS. Elevated risks of contralateral breast cancer in carriers of PVs in high penetrance genes with DCIS confirmed the utility of testing for surgical decision-making.

Second Primary Cancer Risks After Breast Cancer in BRCA1 and BRCA2 Pathogenic Variant Carriers.

Second primary cancer (SPC) risks after breast cancer (BC) in BRCA1/BRCA2 pathogenic variant (PV) carriers are uncertain. We estimated relative and absolute risks using a novel linkage of genetic testing data to population-scale National Disease Registration Service and Hospital Episode Statistics electronic health records. We followed 25,811 females and 480 males diagnosed with BC and tested for germline BRCA1/BRCA2 PVs in NHS Clinical Genetics centers in England between 1995 and 2019 until SPC diagnosis, death, migration, contralateral breast/ovarian surgery plus 1 year, or the 31st of December 2020. We estimated standardized incidence ratios (SIRs) using English population incidences, hazard ratios (HRs) comparing carriers to noncarriers using Cox regression, and Kaplan-Meier 10-year cumulative risks. There were 1,840 BRCA1 and 1,750 BRCA2 female PV carriers. Compared with population incidences, BRCA1 carriers had elevated contralateral BC (CBC; SIR, 15.6 [95% CI, 11.8 to 20.2]), ovarian (SIR, 44.0 [95% CI, 31.4 to 59.9]), combined nonbreast/ovarian (SIR, 2.18 [95% CI, 1.59 to 2.92]), colorectal (SIR, 4.80 [95% CI, 2.62 to 8.05]), and endometrial (SIR, 2.92 [95% CI, 1.07 to 6.35]) SPC risks. BRCA2 carriers had elevated CBC (SIR, 7.70 [95% CI, 5.45 to 10.6]), ovarian (SIR, 16.8 [95% CI, 10.3 to 26.0]), pancreatic (SIR, 5.42 [95% CI, 2.09 to 12.5]), and combined nonbreast/ovarian (SIR, 1.68 [95% CI, 1.24 to 2.23]) SPC risks. Compared with females without BRCA1/BRCA2 PVs on testing, BRCA1 carriers had elevated CBC (HR, 3.60 [95% CI, 2.65 to 4.90]), ovarian (HR, 33.0 [95% CI, 19.1 to 57.1]), combined nonbreast/ovarian (HR, 1.45 [95% CI, 1.05 to 2.01]), and colorectal (HR, 2.93 [95% CI, 1.53 to 5.62]) SPC risks. BRCA2 carriers had elevated CBC (HR, 2.40 [95% CI, 1.70 to 3.40]), ovarian (HR, 12.0 [95% CI, 6.70 to 21.5]), and pancreatic (HR, 3.56 [95% CI, 1.34 to 9.48]) SPC risks. Ten-year cumulative CBC, ovarian, and combined nonbreast/ovarian cancer risks were 16%/6.3%/7.8% (BRCA1 carriers), 12%/3.0%/6.2% (BRCA2 carriers), and 3.6%/0.4%/4.9% (noncarriers). Male BRCA2 carriers had higher CBC (HR, 13.1 [95% CI, 1.19 to 146]) and prostate (HR, 5.61 [95% CI, 1.96 to 16.0]) SPC risks than noncarriers. Survivors of BC carrying BRCA1 and BRCA2 PVs are at high SPC risk. They may benefit from enhanced surveillance and risk-reduction measures.

The INFLUENCE 3.0 model: Updated predictions of locoregional recurrence and contralateral breast cancer, now also suitable for patients treated with neoadjuvant systemic therapy

BackgroundIndividual risk prediction of 5-year locoregional recurrence (LRR) and contralateral breast cancer (CBC) supports decisions regarding personalised surveillance. The previously developed INFLUENCE tool was rebuild, including a recent population and patients who received neoadjuvant systemic therapy (NST). MethodsWomen, surgically treated for nonmetastatic breast cancer, diagnosed between 2012 and 2016, were selected from the Netherlands Cancer Registry. Cox regression with restricted cubic splines was compared to Random Survival Forest (RSF) to predict five-year LRR and CBC risks. Separate models were developed for NST patients. Discrimination and calibration were assessed by 100x bootstrap resampling. ResultsIn the non-NST and NST group, 49,631 and 10,154 patients were included, respectively. Age, mode of detection, histology, sublocalisation, grade, pT, pN, hormonal receptor status ± endocrine treatment, HER2 status ± targeted treatment, surgery ± immediate reconstruction ± radiation therapy, and chemotherapy were significant predictors for LRR and/or CBC in non-NST patients. For NST patients this was similar, but excluding (y)pT and (y)pN status, and including presence of ductal carcinoma in situ, axillary lymph node dissection and pathologic complete response.For non-NST patients, the Cox and RSF models were integrated in the online tool with 5-year AUCs of 0.77 (95%CI:0.77–0.77) and 0.68 (95%CI:0.67–0.68)] for LRR and CBC prediction, respectively. For NST patients, the RSF model performed best (AUCs 0.77 (95%CI:0.76–0.78) and 0.73 (95%CI:0.69–0.76) for LRR and CBC, respectively). Regarding calibration, observed-predicted differences were all <1 %. ConclusionThis INFLUENCE 3.0 models showed moderate performance in LRR and CBC prediction. The models have been made available as online tool to enable clinical decision support regarding personalised follow-up.

A breast sharing technique using the pedicled IMAP flap for delayed breast reconstruction and contralateral symmetrising mammaplasty: A case series and evolution of the surgical technique in selected patients

IntroductionThe ‘breast-sharing’ procedure uses the disposable tissue as a flap to reconstruct the post-mastectomy defect. This enables simultaneous breast reconstruction and contralateral symmetrisation without additional donor site morbidity. However, controversies related to the oncological safety of this procedure have prevented its widespread uptake. We aim to present this technique based on a pedicled internal mammary artery perforator (IMAP) flap and discuss its technical feasibility and oncological safety. Patients and methodsBetween April 2013 and May 2022, a series of 10 consecutive patients underwent a breast-sharing procedure using the pedicled IMAP flap for breast reconstruction. Clinical and surgical aspects of the breast-sharing procedure were analysed. ResultsIn all cases, the breast-sharing technique allowed for simultaneous breast reconstruction and contralateral breast symmetrisation. Immediate complications included two total venous congestions and one hematoma. Three flaps had distal flap congestion. One flap required debridement and local flap reconstruction. All flaps required fat grafting during the secondary procedures to improve breast symmetry. With an average follow-up of 5,6 years, there was no evidence of recurrent disease. All patients were satisfied to very satisfied with the aesthetic outcome of this reconstructive option. ConclusionsThe breast-sharing technique based on the IMAP flap combines breast reconstruction and contralateral symmetrisation with good aesthetic outcomes in selected patients. The flap has a high complication rate related to venous drainage. Flap design modification and using ICG imaging may reduce venous congestion. A secondary venous micro-anastomosis at the axilla is highly recommended for persistent flap congestion. The reported incidence of contralateral breast cancer is low and thus the residual tissue obtained from the contralateral breast mammaplasty can be safely used for breast reconstruction. Level of EvidenceLevel IV

Adjuvant endocrine therapy and risk of contralateral breast cancer: a systematic review and meta-analysis of observational studies.

Randomized clinical trials support reductions in contralateral breast cancer (CBC) risk with use of adjuvant endocrine therapy, however, real-world treatment effects, particularly for subgroups of breast cancer survivors, remain inconclusive. To address this, population-based observational studies of adjuvant endocrine therapy and CBC were synthesized and meta-analyzed. PubMed and Embase databases were systematically searched for observational studies of endocrine therapy use and CBC risk. Random effects meta-analyses estimated summary relative risks (RRs) and 95% confidence intervals (CIs) for associations between endocrine therapy (ever use of tamoxifen and/or aromatase inhibitors (AIs)) and CBC risk. Heterogeneity across studies was assessed using the I2 test. Subgroup analyses were conducted by study design, menopausal status, and CBC estrogen receptor (ER)-status. Seventeen eligible observational studies (n = 287,576 breast cancer survivors) published between 1995 and 2019 were included. Endocrine therapy use was associated with reduced CBC risk (RR:0.62, 95% CI:0.53, 0.73, I2 = 84.8%, p < 0.0001). No heterogeneity was observed by study design (phet = 0.9). Similar reductions were observed in analyses restricted to tamoxifen use. As only two studies assessed AI use, estimates could not be meta-analyzed. In subgroup analyses, there were no differences in CBC risk reduction by menopausal status (phet = 0.22). Endocrine therapy reduced risk of ER-positive (RR:0.55, 95% CI:0.43, 0.70) but not ER-negative CBC (RR:1.26, 95% CI:0.95, 1.66) (phet < 0.001). This meta-analysis of observational studies supports a reduction in CBC risk with endocrine therapy among breast cancer survivors, in concert with evidence synthesized from randomized clinical trials, and highlights differences in endocrine therapy effectiveness by ER-status of CBC.

Cohort profile: a nationwide study in Dutch CHEK2 c.1100delC families using the infrastructure of the HEreditary Breast and Ovarian cancer study Netherlands – Hebon-CHEK2

PurposeCHEK2 c.1100delC is associated with an increased breast cancer risk in women. While this variant is prevalent in the Netherlands (1% in the general population), knowledge of aetiology and prognosis...

Reductions in recurrence in women with early breast cancer entering clinical trials between 1990 and 2009: a pooled analysis of 155 746 women in 151 trials

Distant recurrence in women with oestrogen receptor-positive early breast cancer persists at a constant rate for more than 20 years after diagnosis, with little equivalent data for oestrogen receptor-negative breast cancer. Using the database of the Early Breast Cancer Trialists' Collaborative Group (EBCTCG) we investigated rates of distant breast-cancer recurrence in oestrogen receptor-positive and oestrogen receptor-negative tumours and trends in outcomes over time. In this pooled analysis of randomised controlled trial data, patients in the EBCTCG database of more than 650 000 women in trials of treatment for early-stage breast cancer were screened for eligibility. Women were eligible if they were enrolled between 1990 and 2009 and newly diagnosed with oestrogen receptor-positive breast cancer and scheduled for at least 5 years of endocrine therapy, or oestrogen receptor-negative disease, and if they were younger than 75 years at diagnosis, had a tumour diameter of 50 mm or less, and fewer than ten positive axillary lymph nodes, and no evidence of distant metastases at entry. Trial of neoadjuvant therapy, or those in which adjuvant therapy was unclear, and women with oestrogen receptor-negative, progesterone receptor-positive disease, or those for whom outcome or baseline data were missing were excluded. The primary outcome was time to first distant recurrence as defined by each trial, ignoring any locoregional recurrence or contralateral breast cancer. 10-year risks of distant recurrence by period of diagnosis were compared using Cox regression adjusted for patient and tumour characteristics, trial, and assigned treatment. Of the 652 258 women with early breast cancer in the EBCTCG database on Jan 17, 2023, patient-level data were available from 151 randomised trials that included 155 746 women. Rates of distant tumour recurrence improved similarly in women with oestrogen receptor-positive and oestrogen receptor-negative tumours. 80·5% of the improvement for oestrogen receptor-positive disease and 89·8% of the improvement for eostrogen receptor-negative disease was explained by changes in patient and tumour characteristics and improved treatments, but remained significant (p<0·0001). More recently diagnosed patients were more likely to have node-negative disease. 10-year distant recurrence risks during 1990-99 versus 2000-09 were as follows: for node-negative disease, 10·1% versus 7·3% for oestrogen receptor-positive disease and 18·3% versus 11·9% for oestrogen receptor-negative disease; for disease with one to three positive nodes, 19·9% versus 14·7% for oestrogen receptor-positive disease and 31·9% versus 22·1% for oestrogen receptor-negative disease; and for disease with four to nine positive nodes, 39·6% versus 28·5% for oestrogen receptor-positive disease and 47·8% versus 36·5% for oestrogen receptor-negative disease. After adjustment for therapy, rates were reduced by 25% (oestrogen receptor-positive disease) and 19% (oestrogen receptor-negative disease) after 2000 versus the 1990s, with similar improvements observed in oestrogen receptor-positive disease beyond 5 years. Most of the improvement in trial outcomes is explained by a greater proportion of women with lower-risk disease entering trials and improved adjuvant treatment. After adjustment, women diagnosed since 2000 have about a fifth lower rate of distant recurrence than the 1990s. Long-term risks of distant recurrence for oestrogen receptor-positive disease remain, but are about a tenth lower now than in our previous report. Cancer Research UK, UK Medical Research Council.

Clinical, histological and receptor profiles of invasive breast cancer and ductal carcinoma in situ in females with germline pathogenic variants in PTEN and implications for germline testing

PTEN hamartoma tumour syndrome (PHTS) is an autosomal dominant hereditary cancer syndrome, caused mostly by germline pathogenic variants in PTEN. Female carriers have an up to 80% lifetime risk of breast cancer. Pathologic features of breast cancer in PHTS have seldom been reported. In a collaboration between all histopathology laboratories in our state and our statewide familial cancer service, we tracked the breast biopsies of 12 females with known PTEN pathogenic or likely pathogenic (P/LP) variants (Jan 1990 to Jan 2018). Two further cases were added by a Victorian cancer genetics unit. Breast cancer, inclusive of invasive cancer or ductal carcinoma in situ (DCIS), was diagnosed in 12 of 14 cases (85.7%). One case had a family history of PHTS, and six had a family history of breast cancer. The mean age at first breast cancer diagnosis was 41.6 years (range: 27–63). Six cases developed more than one breast cancer. Five (42%) developed contralateral breast cancer. Ten of the 12 invasive cancers were of no special type, and two were reported as lobular carcinomas. None were grade 1. When reported, all cancers were hormone-receptor positive and HER2 negative. All were associated with DCIS. The DCIS spanned all grades. The two cases without breast cancer still required surgery for exuberant benign changes, including papillomas, fibroadenomatoid change, florid ductal epithelial hyperplasia, adenosis ​and stromal fibrosis. We note that the morphology and receptor profiles of breast cancer in individuals with P/LP PTEN variants are not distinctive. Contrary to prevalent beliefs, these cancers do not conform to the contemporary definition of apocrine breast carcinoma. Greater familiarity of healthcare professionals with the overall clinical and pathologic findings in PHTS and the validated Cleveland Clinic PTEN calculator (http://www.lerner.ccf.org/gmi/ccscore) would improve the recognition of female PHTS individuals with breast cancer. Earlier identification of their cancer predisposition syndrome would benefit these patients and their families who are at high risk of a range of cancers.

Challenges of Contralateral Breast Cancer &amp; Surgical Interventions

Challenges of Contralateral Breast Cancer &amp; Surgical Interventions

AI Use in Mammography for Diagnosing Metachronous Contralateral Breast Cancer.

Although several studies have been conducted on artificial intelligence (AI) use in mammography (MG), there is still a paucity of research on the diagnosis of metachronous bilateral breast cancer (BC), which is typically more challenging to diagnose. This study aimed to determine whether AI could enhance BC detection, achieving earlier or more accurate diagnoses than radiologists in cases of metachronous contralateral BC. We included patients who underwent unilateral BC surgery and subsequently developed contralateral BC. This retrospective study evaluated the AI-supported MG diagnostic system called FxMammo™. We evaluated the capability of FxMammo™ (FathomX Pte Ltd., Singapore) to diagnose BC more accurately or earlier than radiologists' assessments. This evaluation was supplemented by reviewing MG readings made by radiologists. Out of 1101 patients who underwent surgery, 10 who had initially undergone a partial mastectomy and later developed contralateral BC were analyzed. The AI system identified malignancies in six cases (60%), while radiologists identified five cases (50%). Notably, two cases (20%) were diagnosed solely by the AI system. Additionally, for these cases, the AI system had identified malignancies a year before the conventional diagnosis. This study highlights the AI system's effectiveness in diagnosing metachronous contralateral BC via MG. In some cases, the AI system consistently diagnosed cancer earlier than radiological assessments.

Systematic assessment of HER2 status in ductal carcinoma in situ of the breast: a perspective on the potential clinical relevance

In many countries, hormone receptor status assessment of ductal carcinoma in situ (DCIS) is routinely performed, as hormone receptor-positive DCIS patients are eligible for adjuvant anti-hormonal treatment, aiming to reduce the ipsilateral and contralateral breast cancer risk. Although HER2 gene amplification and its associated HER2 protein overexpression constitute a major prognostic and predictive marker in invasive breast carcinoma, its use in the diagnosis and treatment of DCIS is less straightforward. HER2 immunohistochemistry is not routinely performed yet, as the role of HER2-positivity in DCIS biology is unclear. Nonetheless, recent data challenge this practice. Here, we discuss the value of routine HER2 assessment for DCIS. HER2-positivity correlates strongly with DCIS grade: around four in five HER2-positive DCIS show high grade atypia. As morphological DCIS grading is prone to interobserver variability, HER2 immunohistochemistry could render grading more robust. Several studies showed an association between HER2-positive DCIS and ipsilateral recurrence risk, albeit currently unclear whether this is for overall, in situ or invasive recurrence. HER2-positive DCIS tends to be larger, with a higher risk of involved surgical margins. HER2-positive DCIS patients benefit more from adjuvant radiotherapy: it substantially decreases the local recurrence risk after lumpectomy, without impact on overall survival. HER2-positivity in pure biopsy-diagnosed DCIS is associated with increased upstaging to invasive carcinoma after surgery. HER2 immunohistochemistry on preoperative biopsies might therefore provide useful information to surgeons, favoring wider excisions. The time seems right to consider DCIS subtype-dependent treatment, comprising appropriate local treatment for HER2-positive DCIS patients and de-escalation for hormone receptor-positive, HER2-negative DCIS patients.

Detection of Contralateral Malignancies on Breast MRI.

Women with unilateral breast cancer are at increased risk for having simultaneous cancer of the contralateral breast. Overall, earlier detection of contralateral breast cancer prevents the burden of additional surgery or chemotherapy rounds and is associated with higher overall survival. However, MRI screening for the contralateral breast is seldom done following an initial unilateral breast cancer diagnosis. The purpose of this study is to retrospectively evaluate patients with known, biopsy-proven malignancy who went on to obtain a breast MRI and were later found to have cancer of the contralateral breast. Methods: This was a retrospective study that reviewed the charts of women aged over 18 years who were determined to have synchronous bilateral breast cancer from January 2017 to January 2022 at the University of Florida, Gainesville, FL. The study extracted data from this institution's cancer registry database, which provided information on patients with breast cancer diagnoses. The study conducted a review of mammography (MAM) and MRI imaging reports to ascertain the presence or absence of contralateral breast cancer identified by each respective imaging modality. Surgical pathology reports from the biopsy of the contralateral breast were reviewed to obtain information on the histological type of cancer and TNM (tumor, node, metastasis) staging. Of the 17 cases in which MAM missed contralateral cancer, follow-up MRI detected contralateral malignancy in 12 cases (70.59%) and subsequently changed management, resulting in additional imaging, biopsy, and eventual diagnosis and treatment of contralateral breast cancer. Examining the number of contralateral breast cancers detected by patients who had undergone MAM followed by MRI and those who had only undergone MAM, the study found that the detection rate of contralateral breast cancer from MAM was 45.45% (15/33). The tumor stages of the missed cancers were all T1 or Tis stage with one T1mi, and there was no nodal involvement. Conclusion: In addition to its utility in staging breast cancers, MRI also has the superior ability to detect otherwise undetected contralateral breast malignancy. This retrospective study found that MRI imaging led to a considerable increase in the detection of contralateral cancer. The study found that these undetected contralateral breast cancers by MAM were often of lower staging with no nodal involvement, highlighting the opportunity for MRI to assist in early cancer detection while the patient's prognosis is still good. Its high cost should be balanced with staging and occult malignancy detection utility in future practice.

Occurrence of contralateral breast cancer in a BRCA-positive breast cancer patient who underwent free TRAM flap reconstruction: a case report

This report presents a case of contralateral breast cancer in a BRCA mutation-positive patient who had previously undergone delayed free transverse rectus abdominis myocutaneous flap reconstruction for unilateral breast cancer. Having used up the available abdominal autologous tissue in the first reconstruction, a direct-to-implant procedure was employed for the reconstruction of the second, contralateral breast. Therefore, one breast was reconstructed using autologous tissue from the abdomen, while the other was asymmetrically reconstructed with an implant. If the risk of contralateral breast cancer had been anticipated initially, we might have opted for implant-based reconstruction from the start to facilitate a more symmetrical outcome in the event of subsequent contralateral reconstruction. This case underscores the importance of reviewing the risk of contralateral breast cancer in patients with unilateral breast cancer who also carry mutations in BRCA and other breast cancer susceptibility genes. Furthermore, it encourages consideration of how mutations in breast cancer susceptibility genes, including BRCA, influence the choice of plastic surgery reconstruction techniques. The findings from genetic testing for breast cancer susceptibility are now crucial to achieving aesthetic completeness in breast reconstruction.

Impact of contralateral prophylactic mastectomy on survival outcomes in patients with unilateral breast cancer: A systematic review and meta-analysis.

To synthesize contemporary evidence of the impact of contralateral prophylactic mastectomy (CPM) on survival outcomes in patients with unilateral breast cancer (UBC). PubMed, EMBASE and Scopus databases were searched for observational studies published up to November 15, 2023. Random-effects model was used to obtain pooled effect estimates that were reported as hazards ratio (HR) with 95% confidence intervals (CI). The outcomes of interest were overall survival (OS), breast cancer-specific survival (BCSS), recurrence free survival (RFS) and risk of contralateral breast cancer (CBC). Twenty-one studies were included. Most studies had a retrospective design. CPM was associated with significant improvement of OS (HR 0.80, 95% CI: 0.75, 0.85), BCCS (HR 0.82, 95% CI: 0.74, 0.90), and RFS (HR 0.72, 95% CI: 0.60, 0.86) and significantly reduced risk of CBC (HR 0.05, 95% CI: 0.03, 0.09) in patients with UBC. No evidence of publication bias was detected. Our results provide strong evidence supporting the positive impact of CPM on survival outcomes in patients with UBC. Further research and long-term follow-up studies are warranted to validate these findings.

Bilateral Mastectomy and Breast Cancer Mortality

The benefit of bilateral mastectomy for women with unilateral breast cancer in terms of deaths from breast cancer has not been shown. To estimate the 20-year cumulative risk of breast cancer mortality among women with stage 0 to stage III unilateral breast cancer according to the type of initial surgery performed. This cohort study used the Surveillance, Epidemiology, and End Results (SEER) Program registry database to identify women with unilateral breast cancer (invasive and ductal carcinoma in situ) who were diagnosed from 2000 to 2019. Three closely matched cohorts of equal size were generated using 1:1:1 matching according to surgical approach. The cohorts were followed up for 20 years for contralateral breast cancer and for breast cancer mortality. The analysis compared the 20-year cumulative risk of breast cancer mortality for women treated with lumpectomy vs unilateral mastectomy vs bilateral mastectomy. Data were analyzed from October 2023 to February 2024. Type of breast surgery performed (lumpectomy, unilateral mastectomy, or bilateral mastectomy). Contralateral breast cancer or breast cancer mortality during the 20-year follow-up period among the groups treated with lumpectomy vs unilateral mastectomy vs bilateral mastectomy. The study sample included 661 270 women with unilateral breast cancer (mean [SD] age, 58.7 [11.3] years). After matching, there were 36 028 women in each of the 3 treatment groups. During the 20-year follow-up, there were 766 contralateral breast cancers observed in the lumpectomy group, 728 contralateral breast cancers in the unilateral mastectomy group, and 97 contralateral cancers in the bilateral mastectomy group. The 20-year risk of contralateral breast cancer was 6.9% (95% CI, 6.1%-7.9%) in the lumpectomy-unilateral mastectomy group. The cumulative breast cancer mortality was 32.1% at 15 years after developing a contralateral cancer and was 14.5% for those who did not develop a contralateral cancer (hazard ratio, 4.00; 95% CI, 3.52-4.54, using contralateral breast cancer as a time-dependent covariate). Deaths from breast cancer totaled 3077 women (8.54%) in the lumpectomy group, 3269 women (9.07%) in the unilateral mastectomy group, and 3062 women (8.50%) in the bilateral mastectomy group. This cohort study indicates that the risk of dying of breast cancer increases substantially after experiencing a contralateral breast cancer. Women with breast cancer treated with bilateral mastectomy had a greatly diminished risk of contralateral breast cancer; however, they experienced similar mortality rates as patients treated with lumpectomy or unilateral mastectomy.

Contralateral Breast Cancer Remains a Complex Biologic Conundrum

Contralateral Breast Cancer Remains a Complex Biologic Conundrum

Patient-Reported Outcomes 10 Years After Breast-Conserving Surgery for Early-Stage Breast Cancer.

Patient-reported outcomes (PROs) are a critical component of value-based care. Limited data exist describing long-term PROs in patients undergoing breast-conserving surgery (BCS). Patients undergoing surgery for stage 0-III breast cancer at our institution from 2002 to 2012 who agreed to be contacted were invited to participate in a cross-sectional PRO study. Health-related quality of life outcomes using BREAST-Q, EORTC QLQ-C30, and EORTC QLQ-BR45 were collected. Patients reporting chemotherapy within 6 months of receiving the survey were excluded. For this work, we focused on patients who underwent BCS. Multivariable linear regression was performed to identify factors associated with PRO scores, adjusting for age, time since surgery, anatomic stage, molecular subtype, receipt of systemic and/or radiation therapy (RT), locoregional recurrence, or contralateral breast cancer. Among 562 interested and eligible patients, 437 (78%) responded; median time from surgery to survey completion was 10.4 years (interquartile range: 8.0-13.5). Median age at surgery was 53 years (standard deviation 9.8 years), ≥ 90% were white, had upfront surgery for early-stage disease, and completed adjuvant RT. Physical and psychological well-being scores were generally high, with more variation seen for sexual well-being and satisfaction with breasts. This study provides long-term PRO data for patients treated with BCS, demonstrating the ongoing association of breast cancer surgery with quality of life in the survivorship period and highlighting the importance of examining PROs beyond the perioperative period. These data also provide important reference values for the interpretation of PROs among women treated with BCS as we move towards value-based care.

Invasive recurrence after breast conserving treatment of ductal carcinoma in situ of the breast in the Netherlands: time trends and the association with tumour grade.

The first aim of this study was to examine trends in the risk of ipsilateral invasive breast cancer (iIBC) after breast-conserving surgery (BCS) of ductal carcinoma in situ (DCIS). A second aim was to analyse the association between DCIS grade and the risk of iIBC following BCS. In this population-based, retrospective cohort study, the Netherlands Cancer Registry collected information on 25,719 women with DCIS diagnosed in the period 1989-2021 who underwent BCS. Of these 19,034 received adjuvant radiotherapy (RT). Kaplan-Meier analyses and Cox regression models were used. A total of 1135 patients experienced iIBC. Ten-year cumulative incidence rates of iIBC for patients diagnosed in the periods 1989-1998, 1999-2008 and 2009-2021 undergoing BCS without RT, were 12.6%, 9.0% and 5.0% (P < 0.001), respectively. For those undergoing BCS with RT these figures were 5.7%, 3.7% and 2.2%, respectively (P < 0.001). In the multivariable analyses, DCIS grade was not associated with the risk of iIBC. Since 1989 the risk of iIBC has decreased substantially and has become even lower than the risk of invasive contralateral breast cancer. No significant association of DCIS grade with iIBC was found, stressing the need for more powerful prognostic factors to guide the treatment of DCIS.