Rate Of Contralateral Breast Cancer Research Articles

Abstract ED02-02: The Challenges of Lobular Carcinoma

Abstract Infiltrating lobular carcinoma (ILC) and lobular carcinoma in situ (LCIS) were first described in the1940s by two Memorial Hospital pathologists, Foote and Stewart. They were most intrigued by the infiltrative appearance of these lobular cancers which they described as demonstrating large numbers of isolated, loose or dyscohesive cells of rather uniform size but of varying shape. We now recognize that this dyscohesive growth pattern is the result of loss of a functional e-cadherin protein; a distinguishing feature between ILC and invasive ductal carcinoma (IDC). Several studies comparing clinical features and outcomes between ILC and IDC have generated consistent findings. Lobular cancers are more likely to be ER+, larger, lower grade, less likely to be detected on MMG and more likely to have positive margins at breast conserving surgery (BCS), or to require mastectomy. Yet importantly, if BCS is successful, local recurrence and rates of contralateral breast cancer are equal for ILC and IDC. Although lobular cancers represents only 5-15% of all breast cancer, numerically, if ILC was an independent cancer in women, it would rank as the 6th most common cancer in women. Notably the incidence of ILC rose sharply in the late 80s throughout the 90s, and it has become clear that there is a strong relationship between ILC and hormone replacement therapy. Perhaps the “strongest” risk factor for ILC, is LCIS. Classic LCIS is an incidental finding – there are no pathnogmonic features on breast imaging or gross examination of tissue. On microscopic examination it is often multicentric and bilateral. Although originally considered a precursor to ILC and treated with mastectomy, over the years it was realized that rates of ipsilateral cancer in women who were not treated for LCIS were lower than expected and were quite similar to rates of contralateral breast cancer – and this combined with the fact that only 50% of the cancers were of the lobular phenotype led to a movement to consider LCIS as a high risk lesion. Contemporary data continue to support this management approach as rates of cancer development in women with a diagnosis of LCIS are consistently reported at 1-2% per year and the risk is conferred bilaterally, with a slightly higher representation of ILC in the ipsilateral breast. In this presentation we will review areas of clinical controversy, including the use of MRI, the safety of breast conservation, the role of neoadjuvant chemotherapy and the utility of genomic assays in patients with ILC. Citation Format: T. King. The Challenges of Lobular Carcinoma [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr ED02-02.

Abstract PO1-10-01: Racial/Ethnic Disparities in Rates of Pathological Complete Response and Survival in Patients with Inflammatory Breast Cancer

Abstract Radiation Therapy Toxicities and Survival Outcomes in Monoallelic ATM Variant Carriers with Non-Metastatic Breast Cancer: A Retrospective Analysis Rayan Bensenane1 MD, Arnaud Beddok1,2,3 MD, Nadine Andrieu4 PhD, Fabienne Lesueur4 PhD, Eve Cavaciuti 4 MSc, Dorothee Le Gal4 MSc, Eon-Marchais Severine4 PhD, Dominique Stoppa Lyonnet 5MD PhD, Youlia Kirova1 MD 1. Institut Curie, PSL Research University, Radiation Oncology Department, Paris/Saint-Cloud/Orsay, France. 2. Gordon Center for Medical Imaging, Massachusetts General Hospital, Harvard Medical School, 125 Nashua St., Boston, MA, 02114, USA 3. Institut Curie, PSL Research University, University Paris Saclay, Inserm LITO U1288 Orsay, France 4. Inserm, U900, Institut Curie, PSL Research University, Mines ParisTech, Paris, France 5.Department of Genetics, Institut Curie; Inserm U830, Institut Curie; Paris-Cité University Abstract (characters: 2952; max 3400 characters, not include spaces) Background: The Ataxia-Telangiectasia Mutated (ATM) gene, involved in the repair of DNA double-strand breaks, can contribute to radiosensitivity when a bi-allelic variant is present and lead to Ataxia-Telangiectasia syndrome. Moreover, monoallelic ATM pathologic variant (PV) carriers, especially women, has an estimated occurrence rate of 0.5-1% globally and face a 2 to 3-fold increased risk of developing breast cancer. Despite evidence of in vitro radiosensitivity in cells derived from monoallelic variant carriers, there is a dearth of patient studies examining the risk of radiation-induced toxicity. This study aims to explore radiation therapy (RT) toxicities in non-metastatic breast cancer women carrying a germline monoallelic ATM variant, compared to non-carriers. Methods: A retrospective study was conducted on patients treated at Institut Curie, Paris from 1999 to 2014 and participating to CoF-AT (a French national study) and GENESIS database. ATM variant screenings encompassed both PV and non-PV, with toxicities evaluated using CTCAE v.5. Variants were classified as pathogenic, variant of unknown significance (VUS), or benign. Follow-up started from age/date at breast cancer to acute, late toxicities, disease recurrence or last news. Survival and toxicity comparisons were made using Kaplan-Meier survival analysis and Chi-square tests, respectively, with a significance level of α set at 0.05. Results: Among 50 patients, nine were ATM variant carriers (3 PV/5 VUS/1 benign), and 41 were non-carriers. Most patients had no smoking history (68%), and invasive ductal carcinoma was the predominant diagnosis (82%). The majority underwent breast-conservative surgery (80%), and the dominant RT techniques were 3D-Conformational Radiation Therapy (70%) and Isocentric Lateral Decubitus (30%). The median RT dose was 50 Gy over an average period of 36.5 days. With a median follow-up of 12 years post-diagnosis, no significant difference in acute dermatitis, esophagitis, lymphedema, cutaneous fibrosis, telangiectasia, or heart disease was observed between the groups. Analysis of overall survival (OS) showed a 5-year OS of 98%, decreasing to 89% at 10 years. For ATM variant carriers, the OS at 5, 10, and 15 years was 100%, 89%, and 89%, respectively, similar to non-carriers. Kaplan-Meier analysis revealed no significant differences in 5, 10, and 15-year overall survival, progression-free survival, local failure-specific survival, and contralateral breast cancer rates between the groups. Conclusion: In non-metastatic breast cancer patients, monoallelic ATM variant carrier status does not significantly influence acute or late RT toxicities and survival outcomes. These findings, derived from a small cohort, highlight the need for prospective studies for further validation. Table: Acute and Late Toxicities Post-Radiation Therapy in Monoallelic ATM Variant Carriers vs Non-Carriers Citation Format: Rebecca Zasloff, Samantha Thomas, Kendra Parrish, Astrid Botty van de Bruele, Gayle DiLalla, Maggie DiNome, Laura Rosenberger, Hannah Woriax, E Shelley Hwang, Jennifer Plichta, Akiko Chiba. Racial/Ethnic Disparities in Rates of Pathological Complete Response and Survival in Patients with Inflammatory Breast Cancer [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO1-10-01.

Abstract PO1-22-05: Radiation Therapy Toxicities and Survival Outcomes in Monoallelic ATM Variant Carriers with Non-Metastatic Breast Cancer: A Retrospective Analysis

Abstract Radiation Therapy Toxicities and Survival Outcomes in Monoallelic ATM Variant Carriers with Non-Metastatic Breast Cancer: A Retrospective Analysis Rayan Bensenane1 MD, Arnaud Beddok1,2,3 MD, Nadine Andrieu4 PhD, Fabienne Lesueur4 PhD, Eve Cavaciuti 4 MSc, Dorothee Le Gal4 MSc, Eon-Marchais Severine4 PhD, Dominique Stoppa Lyonnet 5MD PhD, Youlia Kirova1 MD 1. Institut Curie, PSL Research University, Radiation Oncology Department, Paris/Saint-Cloud/Orsay, France. 2. Gordon Center for Medical Imaging, Massachusetts General Hospital, Harvard Medical School, 125 Nashua St., Boston, MA, 02114, USA 3. Institut Curie, PSL Research University, University Paris Saclay, Inserm LITO U1288 Orsay, France 4. Inserm, U900, Institut Curie, PSL Research University, Mines ParisTech, Paris, France Abstract (characters: 2952; max 3400 characters, not include spaces) Background: The Ataxia-Telangiectasia Mutated (ATM) gene, involved in the repair of DNA double-strand breaks, can contribute to radiosensitivity when a bi-allelic variant is present and lead to Ataxia-Telangiectasia syndrome. Moreover, monoallelic ATM pathologic variant (PV) carriers, especially women, has an estimated occurrence rate of 0.5-1% globally and face a 2 to 3-fold increased risk of developing breast cancer. Despite evidence of in vitro radiosensitivity in cells derived from monoallelic variant carriers, there is a dearth of patient studies examining the risk of radiation-induced toxicity. This study aims to explore radiation therapy (RT) toxicities in non-metastatic breast cancer women carrying a germline monoallelic ATM variant, compared to non-carriers. Methods: A retrospective study was conducted on patients treated at Institut Curie, Paris from 1999 to 2014 and participating to CoF-AT (a French national study) and GENESIS database. ATM variant screenings encompassed both PV and non-PV, with toxicities evaluated using CTCAE v.5. Variants were classified as pathogenic, variant of unknown significance (VUS), or benign. Follow-up started from age/date at breast cancer to acute, late toxicities, disease recurrence or last news. Survival and toxicity comparisons were made using Kaplan-Meier survival analysis and Chi-square tests, respectively, with a significance level of α set at 0.05. Results: Among 50 patients, nine were ATM variant carriers (3 PV/5 VUS/1 benign), and 41 were non-carriers. Most patients had no smoking history (68%), and invasive ductal carcinoma was the predominant diagnosis (82%). The majority underwent breast-conservative surgery (80%), and the dominant RT techniques were 3D-Conformational Radiation Therapy (70%) and Isocentric Lateral Decubitus (30%). The median RT dose was 50 Gy over an average period of 36.5 days. With a median follow-up of 12 years post-diagnosis, no significant difference in acute dermatitis, esophagitis, lymphedema, cutaneous fibrosis, telangiectasia, or heart disease was observed between the groups. Analysis of overall survival (OS) showed a 5-year OS of 98%, decreasing to 89% at 10 years. For ATM variant carriers, the OS at 5, 10, and 15 years was 100%, 89%, and 89%, respectively, similar to non-carriers. Kaplan-Meier analysis revealed no significant differences in 5, 10, and 15-year overall survival, progression-free survival, local failure-specific survival, and contralateral breast cancer rates between the groups. Conclusion: In non-metastatic breast cancer patients, monoallelic ATM variant carrier status does not significantly influence acute or late RT toxicities and survival outcomes. These findings, derived from a small cohort, highlight the need for prospective studies for further validation. Table: Acute and Late Toxicities Post-Radiation Therapy in Monoallelic ATM Variant Carriers vs Non-Carriers * Pearson/Chi2 test ; NS: non significant at α=0.05; ATM +/+: wild type for ATM; ATM +/- : ATM monoallelic germline variant carrier Citation Format: Rayan BENSENANE, Youlia Kirova, Arnaud BEDDOK, Andine ANDRIEU, Fabienne Lesueur, Eve CAVACIUTI, Dorothée Le GAL, Severine EON-MARCHAIS, Dominique STOPPA LYONNET. Radiation Therapy Toxicities and Survival Outcomes in Monoallelic ATM Variant Carriers with Non-Metastatic Breast Cancer: A Retrospective Analysis [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO1-22-05.

TP53-associated early breast cancer: new observations from a large cohort.

A large well-annotated recent international cohort of Li-Fraumeni (LFS) patients with early-stage breast cancer (BC) was examined for shared features. This multicentre cohort study included females with a germline TP53 pathogenic or likely pathogenic variant and nonmetastatic BC diagnosed between 2002-2022. Clinical and genetic data were obtained from institutional registries and clinical charts. Descriptive statistics were utilized to summarize proportions and differences were assessed by Chi square or Wilcoxon rank sum tests. Metachronous contralateral breast cancer (CBC) risk, radiation-induced sarcoma risk, and recurrence-free survival (RFS) were analyzed by Kaplan-Meier methodology. Among 227 females who met study criteria, the median age of first BC diagnosis was 37 years (range 21-71), 11.9% presented with bilateral synchronous BC and 18.1% had ductal carcinoma in situ (DCIS) only. In total, 166 (73.1%) underwent mastectomies including 67 bilateral mastectomies as first BC surgery. Among those with retained breast tissue, CBC rate was 25.3% at 5-years. Among 186 invasive tumors, 72.1% were stages I-II, 48.9% node-negative, and the most common subtypes were HR+/HER2- (40.9%) and HR+/HER2 + (34.4%). At a median follow-up of 69.9 months (IQR 32.6-125.9), invasive HR+/HER2- disease had the highest recurrence risk among the subtypes (5-year RFS 61.1%, p = .0012). Among those who received radiation therapy (n = 79), the 5-year radiation-induced sarcoma rate was 4.8%. We observed high rates of DCIS, HR+ and HER2+ breast cancers, with a worse outcome in the HR+/HER2- luminal tumors despite appropriate treatment. Confirmation of these findings in further studies could have implications for BC care in LFS.

Age-Related Incidence and Peak Occurrence of Contralateral Breast Cancer

ImportanceYoung patients with breast cancer have higher risk for developing contralateral breast cancer (CBC) and have epidemiologic characteristics different from those of older patients.ObjectiveTo examine the incidence and peak occurrence of CBC according to age at primary breast cancer (PBC) surgery.Design, Setting, and ParticipantsThis cohort study included patients who were diagnosed with and underwent surgery for unilateral nonmetastatic breast cancer at Asan Medical Center, Korea, between January 1, 1999, and December 31, 2013, with follow-up through December 31, 2018. Data were analyzed from December 1, 2021, through April 30, 2023. Patients were divided into 2 groups according to their age at surgery for PBC: younger (≤35 years) vs older (>35 years).Main Outcomes and MeasuresThe main outcomes were cumulative incidence and hazard rate of CBC in the entire study population and in subgroups divided by cancer subtype, categorized according to hormone receptor (HR) and ERBB2 status.ResultsA total of 16 251 female patients with stage 0 to III breast cancer were analyzed; all patients were Korean. The mean (SD) age was 48.61 (10.06) years; 1318 patients (8.11%) were in the younger group, and 14 933 (91.89%) were in the older group. Median follow-up was 107 months (IQR, 79-145 months). Compared with the older group, the younger group had significantly higher incidence of CBC (10-year cumulative incidence, 7.1% vs 2.9%; P < .001) and higher risk (hazard ratio, 2.10; 95% CI, 1.62-2.74) of developing CBC. The hazard rate, which indicates risk for developing CBC at a certain time frame, differed according to the subtype of primary cancer. In patients with the HR+/ERBB2– subtype, the risk increased continuously in both age groups. In patients with the triple negative subtype, the risk increased until approximately 10 years and then decreased in both age groups. Meanwhile, in the HR−/ERBB2+ subtype, risk peaked earlier, especially in the younger group (1.7 years since first surgery in the younger group and 4.8 years in the older group).Conclusions and RelevanceIn this cohort study, patients aged 35 years or younger with breast cancer had a higher risk of developing CBC than older patients. Moreover, young patients with the HR−/ERBB2+ subtype tended to have a shorter interval for developing CBC. These findings might be useful in guiding treatment decisions, such as contralateral prophylactic mastectomy.

Survival After Development of Contralateral Breast Cancer in Korean Patients With Breast Cancer

Contralateral breast cancer (CBC) is the most frequently diagnosed primary cancer in patients with breast cancer. Although many studies have reported survival after the development of CBC, results have been inconsistent. To investigate whether the development of CBC is associated with survival among patients with breast cancer. This cohort study was conducted at the Asan Medical Center, Korea, among patients who were diagnosed with primary unilateral, nonmetastatic, stage 0 to III breast cancer between 1999 and 2013 and followed up through 2018. The median (IQR) follow-up was 107 (75-143) months. Patients were categorized into CBC and no-CBC groups by whether they developed CBC during the follow-up period. Data were analyzed from November 2021 to March 2023. Development of CBC. Survival rates of CBC and no-CBC groups were compared using a time-dependent Cox proportional hazard model in the entire study population and in subgroup analyses by interval of CBC development and subtype of the primary breast cancer. Among 16 251 patients with breast cancer (all Asian, specifically Korean; mean [SD] age, 48.61 [10.06] years), 418 patients developed CBC. There was no significant difference in overall survival between CBC and no-CBC groups (hazard ratio, 1.166; 95% CI, 0.820-1.657). Patients who developed CBC within 1.5 years after the surgery of the primary breast cancer had a higher risk for overall death during the study period (hazard ratio, 2.014; 95% CI, 1.044-3.886), and those who developed CBC after 1.5 years showed no significant difference in survival compared with the no-CBC group. Patients with hormone receptor (HR)-positive and human epidermal growth factor receptor 2 (ERBB2, formerly HER2)-negative breast cancer had a higher risk for overall death in the CBC group (hazard ratio, 1.882; 95% CI, 1.143-3.098) compared with the no-CBC group. This study found that development of CBC in patients with breast cancer was not associated with survival but that early development of CBC after diagnosis of the primary breast cancer or development of CBC in patients with HR-positive/ERBB2-negative breast cancer was associated with survival. These results may provide valuable information for patients seeking advice on opting for contralateral prophylactic mastectomy.

Whole Breast Irradiation in Comparison to Endocrine Therapy in Early Stage Breast Cancer-A Direct and Network Meta-Analysis of Published Randomized Trials.

Multiple randomized trials have established adjuvant endocrine therapy (ET) and whole breast irradiation (WBI) as the standard approach after breast-conserving surgery (BCS) in early-stage breast cancer. The omission of WBI has been studied in multiple trials and resulted in reduced local control with maintained survival rates and has therefore been adapted as a treatment option in selected patients in several guidelines. Omitting ET instead of WBI might also be a valuable option as both treatments have distinctly different side effect profiles. However, the clinical outcomes of BCS + ET vs. BCS + WBI have not been formally analyzed. We performed a systematic literature review searching for randomized trials comparing BCS + ET vs. BCS + WBI in low-risk breast cancer patients with publication dates after 2000. We excluded trials using any form of chemotherapy, regional nodal radiation and mastectomy. The meta-analysis was performed using a two-step process. First, we extracted all available published event rates and the effect sizes for overall and breast-cancer-specific survival (OS, BCSS), local (LR) and regional recurrence, disease-free survival, distant metastases-free interval, contralateral breast cancer, second cancer other than breast cancer and mastectomy-free interval as investigated endpoints and compared them in a network meta-analysis. Second, the published individual patient data from the Early Breast Cancer Trialists' Collaborative Group (EBCTCG) publications were used to allow a comparison of OS and BCSS. We identified three studies, including a direct comparison of BCS + ET vs. BCS + WBI (n = 1059) and nine studies randomizing overall 7207 patients additionally to BCS only and BCS + WBI + ET resulting in a four-arm comparison. In the network analysis, LR was significantly lower in the BCS + WBI group in comparison with the BCS + ET group (HR = 0.62; CI-95%: 0.42-0.92; p = 0.019). We did not find any differences in OS (HR = 0.93; CI-95%: 0.53-1.62; p = 0.785) and BCSS (OR = 1.04; CI-95%: 0.45-2.41; p = 0.928). Further, we found a lower distant metastasis-free interval, a higher rate of contralateral breast cancer and a reduced mastectomy-free interval in the BCS + WBI-arm. Using the EBCTCG data, OS and BCSS were not significantly different between BCS + ET and BCS + WBI after 10 years (OS: OR = 0.85; CI-95%: 0.59-1.22; p = 0.369) (BCSS: OR = 0.72; CI-95%: 0.38-1.36; p = 0.305). Evidence from direct and indirect comparison suggests that BCS + WBI might be an equivalent de-escalation strategy to BCS + ET in low-risk breast cancer. Adverse events and quality of life measures have to be further compared between these approaches.

When to stop? Mammographic surveillance in breast cancer survivors aged 70 years and older

To assess the rates of breast cancer detected in postoperative surveillance mammograms in women >70 Years and overall mortality in this age group. Four hundred and ninety-eight patients were identified retrospectively from a database from a single large UK hospital. Patients were included in the study if they were female, aged >70 years at diagnosis of either invasive breast cancer or ductal carcinoma in situ (DCIS), had surgical treatment between 1 January 2010 and 31 December 2014, and no previous diagnosis of breast cancer. Statistical analysis was performed using Excel, using the X2 test, with p≤0.05 considered statistically significant. The mean age of women included in this study was 77 years. The mean number of postoperative surveillance mammograms performed per patient was 4.2. In the 5-year follow-up, there was a local recurrence rate of 1.9% (n=6) and a contralateral breast cancer rate of 1% (n=6). The 5-year overall mortality rate was 17.7% (n=88), and the 5-year breast cancer-specific mortality rate was 7.2% (n=36). This study demonstrated low local recurrence and contralateral breast cancer rates during the 5-year follow-up period. Clear discussions therefore need to be held with older patients about the value of postoperative mammographic surveillance. Further research is required regarding patient opinion and experience to help develop more consistent guidelines.

Comparing an operation to monitoring, with or without endocrine therapy (COMET), for low-risk ductal carcinoma in situ (DCIS).

TPS616 Background: Approximately 50,000 women in the U.S. are diagnosed with ductal carcinoma in situ (DCIS) each year. Without treatment, it is estimated that only 20-30% of DCIS will lead to invasive breast cancer (IBC). However, over 97% of women are currently treated with surgery +/- radiation. An alternative to surgery is active monitoring (AM), a management approach in which mammograms/physical exams are used to monitor breast changes and determine when, or if, surgery is needed. The COMET Study will compare risks and benefits of AM versus surgery for low-risk DCIS in the setting of a Phase III multicenter prospective randomized trial. The study is funded by the Patient-Centered Outcomes Research Institute. The COMET trial opened in the U.S. in June 2017 (Clinicaltrials.gov reference: NCT02926911). In November 2021, the Data Safety Monitoring Board reviewed the trial and suggested that it continue as planned. Patient accrual will continue until 12/31/2022. Methods: The primary objective is to assess whether the 2-year ipsilateral IBC rate for AM is non-inferior to that for surgery. Secondary objectives include determining whether AM is non-inferior to surgery for 2-year mastectomy rate; breast conservation rate; contralateral breast cancer rate; overall and breast cancer-specific survival. Patient reported outcomes will enable comparison of health-related quality of life and psychosocial outcomes between surgery and AM groups at baseline, 6-months, and years 1-5. Eligibility criteria include: age > 40 at diagnosis; pathologic confirmation of grade I/II DCIS or atypia verging on DCIS without invasion by two pathologists; ER and/or PR ≥ 10%; no mass on physical exam or imaging. The accrual goal is 1200 randomized patients across 100 Alliance for Clinical Trials in Oncology sites. Sample size is estimated using a 2-group test of non-inferiority of proportions, with the 2-year IBC rate in the surgery group assumed to be 0.10 based on published studies and non-inferiority margin of 0.05. Based on a 1-sided un-pooled z-test, with alpha = 0.05, a sample size of n = 446 per group will have 80% power to detect the specified non-inferiority margin. Final analysis plan will include a per protocol component as well as a pragmatic component for patients who are randomized and decline participation in their assigned arm. Primary analyses will adjust for dropout, non-compliance and contamination by utilizing instrumental variable methods. Clinical trial information: NCT02926911.

Isotope-Only Localization for Sentinel Lymph Node Biopsy - Medium-Term Oncological Outcomes

AimsIsotope and blue dye dual localization in sentinel lymph node biopsy (SLNB) gives localization rates of over 98% and is the recommended technique. However blue dye risks a range of adverse reactions. Since 2010, for clinically node negative disease, we have only used blue dye if there is no clear isotope signal at surgery. MethodsElectronic records of patients who underwent isotope-only SLN localization between July 2010 and April 2012 were examined. Data were collected on localization and oncological outcomes. Results426 patients were included. Isotope-only localization rate was 97.4% (415/426). The median follow-up was 63.5 months (IQR: 60.7-70.9). Median age was 57 (IQR: 48-67). Median SLN yield was 2 (range: 1-5). Axillary recurrence rate was 1.4% with median time to recurrence of 39.3 months. In-breast recurrence, distant disease and contralateral breast cancer rates were 2.8%, 7%, and 1.9% respectively and 15 (3.5%) patients died of metastatic breast cancer. ConclusionIsotope-only SLNB has a comparable localization rate to dual isotope/blue dye SLNB and can spare the risk of blue dye adverse reactions. The low axillary recurrence rate, maintained to more than 5 years, confirms that isotope-only SLNB is a feasible and safe alternative to dual blue dye/isotope localization.

Contralateral breast cancer after curative-intent treatment for ductal carcinoma in situ: Rate and associated clinicopathological and imaging risk factors

PurposePatients who have ductal carcinoma in situ (DCIS) are undergoing bilateral mastectomy at increasing rates. One of the reasons is to minimize contralateral breast cancer (CBC) risk. The purpose of this study is to determine the rate of and risk factors associated with CBC in women treated for DCIS. MethodsA retrospective study was performed of women with DCIS at surgery from 2007 to 2014 who had at least five-year follow-up. Patient attributes, imaging findings, histopathology results, and surgical and long-term outcomes were collected. Features associated with a CBC were assessed with multivariable logistic regression models. Results613 women (mean 56 years, range 30–87) with DCIS underwent breast-conserving surgery (BCS) (n = 426), unilateral mastectomy (n = 101), or bilateral mastectomy (n = 86), with mean follow-up of 7.9 years. Of the 527 women who had BCS or unilateral mastectomy, 7.4% (n = 39) developed a CBC (DCIS in 12 and invasive cancer in 27). 4.1% (5/122) of women treated with adjuvant endocrine therapy developed a CBC, compared to 8.4% (34/405) who were not treated (p = .11). Features associated with CBC risk were younger age at menarche (adjusted odds ratio [aOR] of 0.76, p = .03) and low nuclear grade of DCIS (aOR of 5.43 for grade 1 versus 3, p = .01). ConclusionIn women treated for DCIS, the overall rate of CBC was low at 7.4%. Younger age at menarche and low nuclear grade of DCIS had significant associations with higher CBC risk.

Risk of Contralateral Breast Cancer in Women with and without Pathogenic Variants in BRCA1, BRCA2, and TP53 Genes in Women with Very Early-Onset (<36 Years) Breast Cancer

Early age at diagnosis of breast cancer is a known risk factor for hereditary predisposition and some studies show a high risk of contralateral breast cancer in BRCA1 carriers diagnosed at very young ages. However, little is published on the risk of TP53 carriers. 397 women with breast cancer diagnosed <36 years of age were obtained from three sources: (i) a population-based study of 283 women diagnosed sequentially from 1980–1997 in North-West England, (ii) referrals to the Genomic Medicine Department at St Mary’s Hospital from 1990–2018, and (iii) individuals from (i) and the Family History Clinic at Wythenshawe Hospital South Manchester who tested negative for pathogenic variants (PV) in all three genes. Sequencing of BRCA1, BRCA2, and TP53 genes was carried out alongside tests for copy number for PV on all referred women. Rates of contralateral breast cancer were censored at death, last assessment, or risk-reducing mastectomy. In total, 47 TP53, 218 BRCA1, and 132 BRCA2 PV carriers were identified with breast cancer diagnosed aged 35 years and under, as well as a representative sample of 261 not known to carry a PV in BRCA1, BRCA2, and TP53. Annual rates of contralateral breast cancer (and percentage of synchronous breast cancers) were TP53: 7.03% (4.3%), BRCA1: 3.57% (1.8%), and BRCA2: 2.63% (1.5%). In non-PV carriers, contralateral rates in isolated presumed/tested non-carrier cases with no family history were 0.56%, and for those with a family history, 0.69%. Contralateral breast cancer rates are substantial in TP53, BRCA1, and BRCA2 PV carriers diagnosed with breast cancer aged 35 and under. Women need to be advised to help make informed decisions on contralateral mastectomy, guided by life expectancy from their index tumor.

Compliance with multidisciplinary team meeting management recommendations.

The objective of this study was to evaluate patient compliance with management recommendations given by a breast cancer multidisciplinary team (MDT), assess for reasons for noncompliance, and perform an exploratory assessment on breast cancer outcomes in noncompliant patients. A retrospective analysis of prospectively collected data was undertaken for patients selected by their primary clinician to be discussed at the MDT of Breast Cancer Research Centre-WA in Perth between 1st March 2011 and the 28th February 2016. The primary objective was the rate of compliance with MDT management recommendations. Secondary objectives included factors associated with noncompliance, rate of clinical trial uptake, and impact of treatment noncompliance on breast cancer events in a subgroup of early breast cancer (EBC) patients. A total of 2614 MDT management recommendations were made for 925 patients. Overall, 92% were compliant with all recommendations given. Clinical trial recruitment was successful in 84.1%. The reasons given for treatment noncompliance were fear of toxicity, choosing an alternative treatment, and treatment inconvenience. In a subset of 337 EBC patients, there was a significantly higher rate of contralateral breast cancer, distant recurrence, and breast cancer-specific death, P=.0016, in those who were noncompliant. Our study demonstrates a high rate of MDT treatment recommendation compliance and clinical trial recruitment. In a subgroup of EBC patients, noncompliance was associated with significantly worse outcomes. Attention to educating patients to minimize their fear of treatment toxicity and ensuring their understanding of evidence-based treatment may lead to lower rates of noncompliance.

Acute Toxicity and Early Oncological Outcomes After Intraoperative Electron Radiotherapy (IOERT) as Boost Followed by Whole Breast Irradiation in 157 Early Stage Breast Cancer Patients-First Clinical Results From a Single Center.

Introduction: Breast conserving surgery (BCS) followed by postoperative whole breast irradiation (WBI) is the current standard of care for early stage breast cancer patients. Boost to the tumor bed is recommended for patients with a higher risk of local recurrence and may be applied with different techniques. Intraoperative electron radiotherapy (IOERT) offers several advantages compared to other techniques, like direct visualization of the tumor bed, better skin sparing, less inter- and intrafractional motion, but also radiobiological effects may be beneficial. Objective of this retrospective analysis of IOERT as boost in breast cancer patients was to assess acute toxicity and early oncological outcomes.Material and Methods: All patients, who have been irradiated between 11/2014 and 01/2018 with IOERT during BCS were analyzed. IOERT was applied using the mobile linear accelerator Mobetron with a total dose of 10 Gy, prescribed to the 90% isodose. After ensured woundhealing, WBI followed with normofractionated or hypofractionated regimens. Patient reports, including diagnostic examinations and toxicity were analyzed after surgery and 6–8 weeks after WBI. Overall survival, distant progression-free survival, in-breast and contralateral breast local progression-free survival were calculated using the Kaplan-Meier method. Furthermore, recurrence patterns were assessed.Results: In total, 157 patients with a median age of 57 years were evaluated. Postoperative adverse events were mild with seroma and hematoma grade 1–2 in 26% and grade 3 in 0.6% of the patients. Wound infections grade 2–3 occurred in 2.2% and wound dehiscence grade 1–2 in 1.9% of the patients. Six to eight weeks after WBI radiotherapy-dependent acute dermatitis grade 1–2 was most common in 90.9% of the patients. Only 4.6% of the patients suffered from dermatitis grade 3. No grade 4 toxicities were documented after surgery or WBI. 2- and 3-year overall survival and distant progression-free survival, were 97.5 and 93.6, and 0.7 and 2.8%, respectively. In-breast recurrence and contralateral breast cancer rates after 3 years were 1.9 and 2.8%, respectively.Conclusion: IOERT boost during BCS is a safe treatment option with low acute toxicity. Short-term recurrence rates are comparable to previously published data and emphasize, that IOERT as boost is an effective treatment.

Age-specific risks of incident, contralateral and ipsilateral breast cancer among 1776 Polish BRCA1 mutation carriers.

Women with an inherited germline BRCA1 mutation have a high lifetime risk of developing breast cancer. We have previously shown that, among BRCA mutation carriers, incidence rates of breast cancer vary by country of residence. In the current study, we prospectively calculated the cumulative and annual incidence rates of incident breast cancer, contralateral breast cancer and ipsilateral breast cancer recurrence among BRCA1 mutation carriers in Poland. Study subjects comprised a cohort of 1776 Polish women with a BRCA1 mutation who had no prior diagnosis of breast or ovarian cancer at the time of enrollment, the women were followed with a biennial follow-up by questionnaire. Women were followed for an average of 6.1 years (range 0.0-18.2) and 191 new breast cancer cases were diagnosed. The cumulative incidence of breast cancer to age 70 was 52%. The annual risk of breast cancer was estimated at 1.78%; the maximum annual risk was observed between the ages of 30 and 65. Among the 941 women with a prior diagnosis of breast cancer, 106 women developed a contralateral breast cancer. The 20-year cumulative incidence of contralateral breast cancer was 31% and the annual rate of contralateral breast cancer was 1.96%. There were 11 recurrences among the 215 women with breast cancer (ipsilateral breast cancers). The cumulative incidence at 20 years was 17% and the annual rate of an ipsilateral recurrence was 1.03%. Our findings confirm the high annual rates of early-onset incident, contralateral and recurrent breast cancer among Polish BRCA1 mutation carriers. These risk estimates are important in the context of the clinical management of unaffected women as well as in the treatment of newly diagnosed primary breast cancers and can also be used as the basis for the planning of prevention trials.

Comparison of operative to monitoring and endocrine therapy for low-risk DCIS (COMET study).

TPS599Background: Approximately 50,000 women in the U.S. are diagnosed with ductal carcinoma in situ (DCIS) each year. Without treatment, it is estimated that only 20-30% of DCIS will lead to invasive breast cancer. However, over 97% of women are currently treated with guideline-concordant care (GCC) including surgery and/or radiation. An alternative to GCC is active surveillance (AS) which focuses on early detection of invasion rather than “treatment” of DCIS. The COMET study will compare risks and benefits of AS versus GCC in the setting of a Phase III pragmatic prospective randomized clinical trial. The study is funded by the Patient-Centered Outcomes Research Institute (PCORI). Methods: The primary objective is to assess whether the 2-, 5-, and 7-year ipsilateral invasive breast cancer rate for AS is non-inferior to that for GCC. Secondary objectives include determining whether AS is non-inferior to GCC for 2-year mastectomy rate; breast conservation rate; contralateral breast cancer rate; overall and...

Genetic and clinical characteristics in Japanese hereditary breast and ovarian cancer: first report after establishment of HBOC registration system in Japan

The hereditary breast and ovarian cancer (HBOC) registration system of Japan was established by the Japanese HBOC Consortium. The first trial was registered in 2015 in four institutions to which some registration committee members belonged. We analyzed the information of 830 Japanese pedigrees, who underwent BRCA1/2 genetic testing, including mutation carriers with BRCA1 (N = 127) and BRCA2 (N = 115), and their families. The mutation-positive rate was 19.7%. Variants of uncertain significance were found in 6.5% of all individuals subjected to genetic testing for BRCA1/2. Compared to the United States, Japan had a higher mutation-positive rate in most categories, except for the groups with male breast cancer. Among the intrinsic subtypes of BRCA1-associated breast cancers, 75.8% were triple-negative. The incidence rate of contralateral breast cancer in BRCA1/2 mutation carriers was 0.99%/year. Among 240 mutation carriers, 26 and 62 patients underwent risk-reducing mastectomy (RRM) and risk-reducing salpingo-oophorectomy (RRSO), respectively; the respective frequencies of occult cancer were 7.1 and 3.2%. Metachronous breast cancer after RRM or peritoneal cancer after RRSO was not observed during the follow-up period. The nationwide registration system began last year and the system enables follow-up analysis in Japan.

Contralateral Breast Cancer Risk in Women with Ductal Carcinoma In Situ: Is it High Enough to Justify Bilateral Mastectomy?

Women with ductal carcinoma in situ (DCIS) are increasingly choosing bilateral mastectomy. We sought to quantify rates of contralateral breast cancer (CBC) and ipsilateral breast tumor recurrence (IBTR) after breast-conserving surgery (BCS) for DCIS, and to compare risk factors for CBC and IBTR. From 1978 to 2011, DCIS patients undergoing BCS with a contralateral breast at risk were identified from a prospectively maintained database. The association of clinicopathologic and treatment factors with CBC and IBTR were evaluated using Kaplan-Meier analysis, multivariable Cox regression, and competing risk regression (CRR). Of 2759 patients identified, 151 developed CBC and 344 developed IBTR. Five- and 10-year Kaplan-Meier CBC rates were 3.2 and 6.4%. Overall, 10-year IBTR rates were 2.5-fold higher than CBC rates, and, without radiation, 4-fold higher. On CRR, 5- and 10-year rates were 2.9 and 5.8% for CBC, and 7.8 and 14.5% for IBTR. CBC risk and invasive CBC risk were not significantly associated with age, family history, presentation, nuclear grade, year of surgery, or radiation. By multivariable Cox regression, endocrine therapy was associated with lower CBC risk (hazard ratio 0.57, p=0.03). Ten-year risk of subsequent CBC in the subset of patients who developed IBTR was similar to the cohort as a whole (8.1 vs. 6.4%). CBC rates were low across all groups, including those who experienced IBTR. CBC was not associated with factors that increase IBTR risk. While factors associated with IBTR risk are important in decision making regarding management of the index DCIS, they are not an indication for contralateral prophylactic mastectomy.

Age, molecular subtypes and local therapy decision-making

The relationship between age and breast cancer subtype is complex: both impact risk of locoregional recurrence (LRR) and survival. Young patients frequently present with aggressive tumors but the increased risk imparted by young age appears to differ among breast cancer subtypes. Dramatic improvements in local control among young women with breast cancer of all tumor subtypes have been observed, likely attributable to improved local therapy strategies, improvements in adjuvant therapies and implementation of subtype-specific targeted therapies. In the light of these improvements in local control, accumulating evidence demonstrates that there is no difference in LRR or survival between breast conserving therapy (BCT) and mastectomy in young patients. An increased risk of LRR in triple-negative cancers is apparent; yet this increased risk of LRR is present following surgical treatment with both BCT and mastectomy and does not significantly differ by age. Also, contralateral breast cancer rates remain low for all age groups and, although the use of contralateral prophylactic mastectomy (CPM) has increased, there is no evidence that CPM improves survival. At the other end of the age spectrum, there is a growing body of evidence demonstrating a favorable interaction between older age and molecular subtype such that many older women with estrogen receptor positive breast cancer may be spared axillary staging and/or radiation therapy without a detrimental impact on survival. Thus for both age and subtype, it appears that the intrinsic biology is the strongest predictor of outcome. Tumor biology, and not age, should be the driver in local therapy decision-making.

Bilateral Mastectomy as Overtreatment for Breast Cancer in Women Age Forty Years and Younger with Unilateral Operable Invasive Breast Cancer.

Young women with breast cancer (BC) have an increased risk of contralateral breast cancer (CBC) compared with older women. This may contribute to the rising rates of bilateral mastectomy (BM), but it is unclear if BM leads to improved outcomes. A prospectively maintained database was reviewed. Patient and tumor characteristics, survival, and rate of CBC were compared in women age≤40years treated for unilateral Stage 1-3 BC from January 2000 through December 2013. Patients ranged in age from 20 to 40 (mean 36) years. Of the 446 women, 188 had breast conservation surgery (BCS), 78 had unilateral mastectomy (UM), and 183 had BM. UM, BCS, and BM groups did not differ in mean age, tumor type, hormone receptor status, or Her2 status. Patients in the BCS and BM group had smaller, fewer node-positive (p=0.02) and lower grade tumors (p<0.01) compared with the UM group. With a median follow-up of 79months, Disease-free survival was similar for patients treated with BM, BCS (p=0.22), or UM (p=0.75). OS was significantly worse in the patients treated with UM (0.02) but was not different between the BCS and BM groups. CBC incidence was 2% (5/263) in patients who underwent BCS or UM, and 0.4% (1/244) in patients without a germline genetic mutation. BCS and UM resulted in similar disease-free survival (DFS) as BM in patients age 40years and younger with BC. BCS and BM had similar OS, whereas UM patients had worse OS. Invasive CBC incidence was less than 0.5% at 10years in patients without identified germline genetic mutations.