Contralateral Breast Cancer Research Articles

How to close the care gap: Factors hindering the use of BRCA mutation profiling of patients with breast cancer and ovarian cancer in a real world setting.

e18636 Background: The majority of hereditary breast and ovarian cancers are linked to BRCA1/2 mutations. However, in patients with a suggestive personal or family history, a specific predisposing gene is identified in < 30% of cases. Mutation testing is recommended for individual genes in the appropriate clinical setting with a high suspicion index for a specific mutated gene. The risk of contralateral breast cancer increases with the time since the first breast cancer, reaching 20%–30% at ten years of follow-up and 40%–50% at 20 years, depending on the gene involved. Methods: The study assessed the prevalence of BRCA testing among young breast cancer women (age less than 50 years) and explored the factors hindering the performance of the BRCA mutation test. Among the 3400 breast cancers reported from 2017 to 2022, 46.17% (n = 1570) of young breast cancer women were advised for BRCA testing. We administered the questionnaire on factors influencing the BRCA mutation profiling performance to all the young breast cancer women (n = 1532). The data was collected from the electronic medical records and the department of molecular oncology. We performed regression analysis to predict the act of BRCA mutation profile testing. Results: Among them (n = 1570), only 17.70% (n = 278) performed BRCA1/2 genetic testing. In 278 patients who had undergone BRCA testing, pathogenic or likely pathogenic BRCA1/2/HRR mutations were detected in 52 patients (18.7%). 38 (13.7%) with BRCA 1, 14(5%) with BRCA2. Somatic with HRR testing was done in 13(4.6%), Somatic testing in 37(13.3%) and germline testing was done in 228 (82%). BRCA mutation was detected in 18 (34.6%) patients with breast cancer, 32(61.5%) patients with ovarian cancer. The factors influencing not performing the BRCA testing were the higher Cost of the test (83.4%), delay in getting the result (32.4%), unawareness of the importance of the test (52.6%), and not being advised by the physician as a mandatory test to perform (47.6%) and male spouse as a decision maker (31.8%). Conclusions: BRCA mutation profile test is mandatory to know their recurrence risk and treatment decisions for opting for PARP inhibitor. But the Cost of the test is the main barrier to performing this in a low-middle-income country setting. Female gender and related decision-making conflict could be the other reasons not to perform the test.

African American women who carry the BRCA1/2 mutation: Clinical characteristics and prevention strategies.

10554 Background: Carriers of pathogenic variants (PV) in BRCA1/2 have an increased risk of breast, ovarian, and other cancers . The clinical characteristics and uptake of risk-reducing interventions in African American(AA) women with BRCA1/2 PVs are less well studied. Methods: After IRB approval, we performed a retrospective chart review on African American women seen at Nancy and James Grosfeld Cancer Genetics Center at Beaumont Health from January 1, 2006, to December 31, 2021, who tested positive for a BRCA 1/2 mutation. We analyzed demographics, cancer characteristics, outcomes, and prevention strategies. Results: Of 238 African American(AA) women who underwent genetic testing, 69 patients (29%) were identified to be a carrier of BRCA1/2 PVs or likely pathogenic variants (LPVs). The median age at testing was 49 years (range: 24-87). Forty-six women (67%) had a cancer diagnosis, with a median age at diagnosis of 52 years. Four women had two, and one had three cancers, for a total of 52 cancers. Breast cancer was the most common type of cancer (40; 77%), with a median age at diagnosis of 48 years (range 24-73) and a majority (26; 65%) being BRCA2 carriers. Most were invasive ductal carcinoma (87.8%), high-grade (80%), ER-positive (52%), PR-negative (68%), HER2-negative (94%) and stage I or II disease (63%). Fifteen (38%) were triple-negative. Most patients (87%) received adjuvant systemic chemotherapy or endocrine therapy, 31% received neoadjuvant chemotherapy, and 39% received adjuvant radiation. The 3- and 5-year survival was 94% and 91%, respectively, with a median follow-up of 103 months. Three patients (all BRCA2 carriers ) developed contralateral breast cancer (median time to recurrence: 201 months); 3 (all BRCA2) developed local recurrence (median time to recurrence: 60 months), and 4(2 BRCA1, 2 BRCA2) developed metastatic recurrence (median time to recurrence: 34 months). Other cancers observed were ovarian (n = 6; 4 BRCA2, 2 BRCA1), uterine (2), lung (2), kidney (1), and glioblastoma (1). Compared to AA carriers without cancer, those with cancer were more likely to undergo risk-reducing mastectomy (RRM; 68% vs. 23%) and risk-reducing salpingo-oophorectomy (RRSO; 72% vs. 55%). In the non-cancer group, significantly fewer patients elected RRM (23%) compared to RRSO (55%). Conclusions: Our study outlines the characteristics of AA women who carry BRCA1/2 PVs, revealing that most had high-grade invasive ductal breast cancer with excellent survival. Patients without a cancer diagnosis were less likely to undergo risk-reducing surgery, highlighting the importance of effective counseling focusing on primary prevention in these high-risk patients. Further research is needed to better characterize cancer risk and address potential barriers to uptake of risk-reducing interventions in this population.

The performance of contrast-enhanced mammography and breast MRI in local preoperative staging of invasive lobular breast cancer

PurposeBreast MRI is considered the best modality for preoperative staging of invasive lobular carcinoma (ILC). However, contrast-enhanced mammography (CEM) shows comparable diagnostic performance to MRI, but evidence of CEM’s accuracy in women diagnosed with ILC is scant. We aimed to retrospectively evaluate CEM and MRI accuracy in preoperative staging of ILC. MethodsILC cases diagnosed between 2013 and 2021 were collected. For both modalities, tumour diameter was extracted from the reports. Bland-Altman plots were used to assess discrepancies between size measurements according to imaging and histopathological findings. CEM and MRI’s ability to detect multifocal/contralateral cancer was expressed as sensitivity, specificity, and diagnostic odds ratios (DORs). Pairwise comparison of women undergoing both CEM and MRI was not performed. Results305 ILC-cases fulfilled preset inclusion criteria. Mean age was 63.7 years. Preoperative staging was performed using MRI or CEM in 266 (87.2%) and 77 (25.2%) cases, respectively. MRI and CEM overestimated tumour size by 1.5 and 2.1 mm, respectively. Sensitivity to detect multifocal disease was higher for MRI than for CEM (86% versus 78%), but specificity was lower for MRI (79% versus 92%). For detection of contralateral breast cancer, sensitivity for MRI was 96% versus 88% for CEM, and specificity was 92% and 99%, respectively. For both indications, DOR was higher for CEM, but differences were non-significant (p = 0.56 and p = 0.78). ConclusionCEM and MRI overestimate ILC size with comparable systematic and random errors. MRI’s higher sensitivity for detection of multifocal/contralateral cancers is accompanied by lower specificity, but discriminative ability for both modalities was non-significant.

Interrupting Endocrine Therapy to Attempt Pregnancy after Breast Cancer

BackgroundProspective data on the risk of recurrence among women with hormone receptor–positive early breast cancer who temporarily discontinue endocrine therapy to attempt pregnancy are lacking.MethodsWe conducted a single-group trial in which we evaluated the temporary interruption of adjuvant endocrine therapy to attempt pregnancy in young women with previous breast cancer. Eligible women were 42 years of age or younger; had had stage I, II, or III disease; had received adjuvant endocrine therapy for 18 to 30 months; and desired pregnancy. The primary end point was the number of breast cancer events (defined as local, regional, or distant recurrence of invasive breast cancer or new contralateral invasive breast cancer) during follow-up. The primary analysis was planned to be performed after 1600 patient-years of follow-up. The prespecified safety threshold was the occurrence of 46 breast cancer events during this period. Breast cancer outcomes in this treatment-interruption group were compared with those in an external control cohort consisting of women who would have met the entry criteria for the current trial.ResultsAmong 516 women, the median age was 37 years, the median time from breast cancer diagnosis to enrollment was 29 months, and 93.4% had stage I or II disease. Among 497 women who were followed for pregnancy status, 368 (74.0%) had at least one pregnancy and 317 (63.8%) had at least one live birth. In total, 365 babies were born. At 1638 patient-years of follow-up (median follow-up, 41 months), 44 patients had a breast cancer event, a result that did not exceed the safety threshold. The 3-year incidence of breast cancer events was 8.9% (95% confidence interval [CI], 6.3 to 11.6) in the treatment-interruption group and 9.2% (95% CI, 7.6 to 10.8) in the control cohort.ConclusionsAmong select women with previous hormone receptor–positive early breast cancer, temporary interruption of endocrine therapy to attempt pregnancy did not confer a greater short-term risk of breast cancer events, including distant recurrence, than that in the external control cohort. Further follow-up is critical to inform longer-term safety. (Funded by ETOP IBCSG Partners Foundation and others; POSITIVE ClinicalTrials.gov number, NCT02308085.)

Risk of second primary cancer among women in the Kaiser Permanente Breast Cancer Survivors Cohort

BackgroundBreast cancer survivors are living longer due to early detection and advances in treatment and are at increased risk for second primary cancers. Comprehensive evaluation of second cancer risk among patients treated in recent decades is lacking.MethodsWe identified 16,004 females diagnosed with a first primary stage I-III breast cancer between 1990 and 2016 (followed through 2017) and survived ≥ 1 year at Kaiser Permanente (KP) Colorado, Northwest, and Washington. Second cancer was defined as an invasive primary cancer diagnosed ≥ 12 months after the first primary breast cancer. Second cancer risk was evaluated for all cancers (excluding ipsilateral breast cancer) using standardized incidence ratios (SIRs), and a competing risk approach for cumulative incidence and hazard ratios (HRs) adjusted for KP center, treatment, age, and year of first cancer diagnosis.ResultsOver a median follow-up of 6.2 years, 1,562 women developed second cancer. Breast cancer survivors had a 70% higher risk of any cancer (95%CI = 1.62–1.79) and 45% higher risk of non-breast cancer (95%CI = 1.37–1.54) compared with the general population. SIRs were highest for malignancies of the peritoneum (SIR = 3.44, 95%CI = 1.65–6.33), soft tissue (SIR = 3.32, 95%CI = 2.51–4.30), contralateral breast (SIR = 3.10, 95%CI = 2.82–3.40), and acute myeloid leukemia (SIR = 2.11, 95%CI = 1.18–3.48)/myelodysplastic syndrome (SIR = 3.25, 95%CI = 1.89–5.20). Women also had elevated risks for oral, colon, pancreas, lung, and uterine corpus cancer, melanoma, and non-Hodgkin lymphoma (SIR range = 1.31–1.97). Radiotherapy was associated with increased risk for all second cancers (HR = 1.13, 95%CI = 1.01–1.25) and soft tissue sarcoma (HR = 2.36, 95%CI = 1.17–4.78), chemotherapy with decreased risk for all second cancers (HR = 0.87, 95%CI = 0.78–0.98) and increased myelodysplastic syndrome risk (HR = 3.01, 95%CI = 1.01–8.94), and endocrine therapy with lower contralateral breast cancer risk (HR = 0.48, 95%CI = 0.38–0.60). Approximately 1 in 9 women who survived ≥ 1 year developed second cancer, 1 in 13 developed second non-breast cancer, and 1 in 30 developed contralateral breast cancer by 10 years. Trends in cumulative incidence declined for contralateral breast cancer but not for second non-breast cancers.ConclusionsElevated risks of second cancer among breast cancer survivors treated in recent decades suggests that heightened surveillance is warranted and continued efforts to reduce second cancers are needed.

Three-Fraction Accelerated Partial Breast Irradiation (APBI) Delivered With Interstitial Brachytherapy Is Safe: First Results From the Tri-fraction Radiation Therapy Used to Minimize Patient Hospital Trips (TRIUMPH-T) Trial

Shorter courses of breast radiotherapy are offered as an alternative to 4 weeks of whole-breast irradiation after lumpectomy, including brachytherapy. A prospective phase 2multi-institution clinical trial to study 3-fraction accelerated partial breast irradiation delivered by brachytherapy was conducted. The trial treated selected breast cancers after breast-conserving surgery with brachytherapy applicators that delivered 22.5 Gy in 3 fractions of 7.5 Gy. The planning treatment volume was 1 to 2 cm beyond the surgical cavity. Eligible women were age ≥45 years with unicentric invasive or in situ tumors ≤3 cm excised with negative margins and with positive estrogen or progesterone receptors and no metastases to axillary nodes. Strict dosimetric parameters were required to be met and follow up information was collected from the participating sites. Two hundred patients were prospectively enrolled; however, a total of 185 patients who were enrolled were followed for a median of 3.63 years. Three-fraction brachytherapy was associated with low chronic toxicity. There was excellent or good cosmesis in 94% of patients. There were no grade 4 toxicities. Grade 3 fibrosis at the treatment site was present in 1.7% and 32% percent had grades 1 or 2 fibrosis at the treatment site. There was 1 rib fracture. Other late toxicities included 7.4% grade 1 hyperpigmentation, 2% grade 1 telangiectasias, 1.7% symptomatic seromas, 1.7% abscessed cavities, and 1.1% symptomatic fat necrosis. There were 2 (1.1%) ipsilateral local recurrences, 2 (1.1%) nodal recurrences and no distant recurrences. Other incidents included one contralateral breast cancer and 2 second malignancies (lung). Ultra-short breast brachytherapy is feasible and has excellent toxicity and could be an alternative to standard 5-day, 10 fraction accelerated partial breast irradiation in eligible patients. Patients from this prospective trial will continue to be followed to evaluate long-term outcomes.

Detection of pathogenic variants in breast cancer susceptibility genes in bilateral breast cancer

PurposeTo investigate the frequency of germline pathogenic variants (PVs) in women with bilateral breast cancer.MethodsWe undertook BRCA1/2 and CHEK2 c.1100delC molecular analysis in 764 samples and a multigene panel in...

Caveolin-1 genotypes as predictor for locoregional recurrence and contralateral disease in breast cancer

PurposeCaveolin-1 (CAV1) has been implicated in breast cancer oncogenesis and metastasis and may be a potential prognosticator, especially for non-distant events. CAV1 functions as a master regulator of membrane transport and cell signaling. Several CAV1 SNPs have been linked to multiple cancers, but the prognostic impact of CAV1 SNPs in breast cancer remains unclear. Here, we investigated CAV1 polymorphisms in relation to clinical outcomes in breast cancer.MethodsA cohort of 1017 breast cancer patients (inclusion 2002–2012, Sweden) were genotyped using Oncoarray by Ilumina. Patients were followed for up to 15 years. Five out of six CAV1 SNPs (rs10256914, rs959173, rs3807989, rs3815412, and rs8713) passed quality control and were used for haplotype construction. CAV1 genotypes and haplotypes in relation to clinical outcomes were assessed with Cox regression and adjusted for potential confounders (age, tumor characteristics, and adjuvant treatments).ResultsOnly one SNP was associated with lymph node status, no other SNPs or haplotypes were associated with tumor characteristics. The CAV1 rs3815412 CC genotype (5.8% of patients) was associated with increased risk of contralateral breast cancer, adjusted hazard ratio (HRadj) 4.26 (95% CI 1.86–9.73). Moreover, the TTACA haplotype (13% of patients) conferred an increased risk for locoregional recurrence HRadj 2.24 (95% CI 1.24–4.04). No other genotypes or haplotypes were associated with clinical outcome.ConclusionCAV1 polymorphisms were associated with increased risk for locoregional recurrence and contralateral breast cancer. These findings may identify patients that could derive benefit from more tailored treatment to prevent non-distant events, if confirmed.

Optimum duration of extended adjuvant endocrine therapy in patients with hormone receptor-positive breast cancer: protocol for a network meta-analysis of randomised controlled trials

IntroductionThe type of extended adjuvant endocrine therapy is not clear, nor is the optimum duration of extended adjuvant endocrine therapy for patients with early breast cancer. Our study aims to...

P162 Contralateral Breast Cancer in BRCA 1 vs 2 Mutation Carriers

P162 Contralateral Breast Cancer in BRCA 1 vs 2 Mutation Carriers

Prospective Pilot Study of 18F-Fluoroestradiol PET/CT in Patients With Invasive Lobular Carcinomas.

BACKGROUND. PET/CT with 18F-fluoroestradiol (FES) (FDA-approved in 2020) depicts tissues expressing estrogen receptor (ER). Invasive lobular carcinoma (ILC) is commonly ER positive. OBJECTIVE. The primary aim of this study was to assess the frequency with which sites of histologically proven ILC have abnormal uptake on FES PET/CT. METHODS. This prospective single-center pilot study, conducted from December 2020 to August 2021, enrolled patients with histologically confirmed ILC to undergo FES PET/CT; patients optionally underwent FDG PET/CT. Two nuclear radiologists assessed FES PET/CT and FDG PET/CT studies for abnormal uptake corresponding to known ILC sites at enrollment and for additional sites of abnormal uptake, resolving differences by consensus. The primary endpoint was percentage of known ILC sites showing abnormal FES uptake. The alternative to the null hypothesis was that more than 60% of sites would have abnormal FES uptake, exceeding the percentage of ILC with abnormal FDG uptake described in prior literature. A sample size of 24 biopsied lesions was preselected to provide 81% power for the alternative hypothesis (one-sided α = .10). Findings on FES PET/CT and FDG PET/CT were summarized for additional secondary endpoints. RESULTS. The final analysis included 17 patients (mean age, 59.1 ± 13.2 years) with 25 sites of histologically confirmed ILC at enrollment (22 breast lesions, two axillary lymph nodes, one distant metastasis). FES PET/CT showed abnormal uptake in 22 of 25 (88%) lesions, sufficient to reject the null hypothesis (p = .002). Thirteen patients underwent FDG PET/CT. Four of 23 (17%) sites of histologically confirmed ILC, including additional sites detected and confirmed after enrollment, were identified with FES PET/CT only, and 1 of 23 (4%) was identified only with FDG PET/CT (p = .18). FES PET/CT depicted additional lesions not detected with standard-of-care evaluation in 4 of 17 (24%) patients (two contralateral breast cancers and two metastatic axillary lymph nodes, all with subsequent histologic confirmation). Use of FES PET/CT resulted in changes in clinical stage with respect to standard-of-care evaluation in 3 of 17 (18%) patients. CONCLUSION. The primary endpoint of the trial was met. The frequency of abnormal FES uptake among sites of histologically known ILC was found to be to be significantly greater than 60%. CLINICAL IMPACT. This pilot study shows a potential role of FES PET/CT in evaluation of patients with ILC. TRIAL REGISTRATION. ClinicalTrials.gov NCT04252859.

Randomized Placebo Controlled Trial of Low-Dose Tamoxifen to Prevent Recurrence in Breast Noninvasive Neoplasia: A 10-Year Follow-Up of TAM-01 Study.

Five-year data of the phase III trial TAM-01 showed that low-dose tamoxifen at 5 mg once daily administered for 3 years in women with intraepithelial neoplasia (IEN) reduced by 52% the recurrence of invasive breast cancer or ductal carcinoma in situ (DCIS), without additional adverse events over placebo. Here, we present the 10-year results. We randomly assigned 500 women with breast IEN (atypical ductal hyperplasia, lobular carcinoma in situ [LCIS], or hormone-sensitive or unknown DCIS) to low-dose tamoxifen or placebo after surgery with or without irradiation. The primary end point was the incidence of invasive breast cancer or DCIS. The TAM-01 population included 500 women (20% atypical ductal hyperplasia, 11% LCIS, and 69% DCIS). The mean (±SD) age at the start of treatment was 54 ± 9 years, and 58% of participants were postmenopausal. After a median follow-up of 9.7 years (IQR, 8.3-10.9 years), 66 breast cancers (15 in situ; 51 invasive) were diagnosed: 25 in the tamoxifen group and 41 in the placebo group (annual rate per 1,000 person-years, 11.3 with tamoxifen v 19.5 with placebo; hazard ratio [HR], 0.58; 95% CI, 0.35 to 0.95; log-rank P = .03). Most recurrences were invasive (77%) and ipsilateral (59%). Regarding contralateral breast cancer incidence, there were six events in the tamoxifen arm and 16 in the placebo arm (HR, 0.36; 95% CI, 0.14 to 0.92; P = .025). The number needed to be treated to prevent one case of breast event with tamoxifen therapy was 22 in 5 years and 14 in 10 years. The benefit was seen across all patient subgroups. There was a significant 50% reduction of recurrence with tamoxifen in the DCIS cohort, which represents 70% of the overall population (HR, 0.50; 95% CI, 0.28 to 0.91; P = .02). No between-group difference in the incidence of serious adverse events was reported during the prolonged follow-up period. Tamoxifen 5 mg once daily for 3 years significantly prevents recurrence from noninvasive breast cancer after 7 years from treatment cessation without long-term adverse events.

Bilateral Breast Cancer: Clinical Profile and Management.

There is paucity of literature regarding the demography, histopathology, management, and outcomes of bilateral breast cancer (BBC). We present our experience of treating 127 BBC with multimodality management. An audit of prospectively maintained computerized breast cancer database of the department of surgical oncology at a tertiary care center was performed. Demography, clinical profile, molecular sub-types, treatment patterns, and outcomes were analyzed. A total 127 patients presented with BBC between 1992 and 2019. Ninety-four had metachronous (MBBC) and 33 had synchronous breast cancer (SBBC). Most contralateral breast cancer (CBC) patients had early-stage breast cancer in comparison to the index side cancer (37% vs 32%). Ninety-four patients underwent bilateral mastectomy and only 18 patients underwent bilateral breast conservation. Seventy-one patients undergoing BCS and surgery for LABC were given postoperative radiotherapy. All patients received adjuvant chemo- and/or hormonal therapy both for index and CBC based on the stage and hormone receptor status. Thirty-three percent of patients had either locoregional or distant relapse. The 5-year overall survival (OS) and 5-year disease-free survival (DFS) of the entire cohort were 86.6% and 68.4% respectively. There was no difference in the OS and DFS between SBBC and MBBC. The incidence of BBC is expected to increase with effective diagnostic and therapeutic interventions and improving survival. Patients require individualized treatment planning in a multidisciplinary treatment setting.

Breast Cancer Risk and Breast-Cancer-Specific Mortality following Risk-Reducing Salpingo-Oophorectomy in BRCA Carriers: A Systematic Review and Meta-Analysis

Risk-reducing salpingo-oophorectomy (RRSO) is the gold standard method of ovarian cancer risk reduction, but the data are conflicting regarding the impact on breast cancer (BC) outcomes. This study aimed to quantify BC risk/mortality in BRCA1/BRCA2 carriers after RRSO. We conducted a systematic review (CRD42018077613) of BRCA1/BRCA2 carriers undergoing RRSO, with the outcomes including primary BC (PBC), contralateral BC (CBC) and BC-specific mortality (BCSM) using a fixed-effects meta-analysis, with subgroup analyses stratified by mutation and menopause status. RRSO was not associated with a significant reduction in the PBC risk (RR = 0.84, 95%CI: 0.59-1.21) or CBC risk (RR = 0.95, 95%CI: 0.65-1.39) in BRCA1 and BRCA2 carriers combined but was associated with reduced BC-specific mortality in BC-affected BRCA1 and BRCA2 carriers combined (RR = 0.26, 95%CI: 0.18-0.39). Subgroup analyses showed that RRSO was not associated with a reduction in the PBC risk (RR = 0.89, 95%CI: 0.68-1.17) or CBC risk (RR = 0.85, 95%CI: 0.59-1.24) in BRCA1 carriers nor a reduction in the CBC risk in BRCA2 carriers (RR = 0.35, 95%CI: 0.07-1.74) but was associated with a reduction in the PBC risk in BRCA2 carriers (RR = 0.63, 95%CI: 0.41-0.97) and BCSM in BC-affected BRCA1 carriers (RR = 0.46, 95%CI: 0.30-0.70). The mean NNT = 20.6 RRSOs to prevent one PBC death in BRCA2 carriers, while 5.6 and 14.2 RRSOs may prevent one BC death in BC-affected BRCA1 and BRCA2 carriers combined and BRCA1 carriers, respectively. RRSO was not associated with PBC or CBC risk reduction in BRCA1 and BRCA2 carriers combined but was associated with improved BC survival in BC-affected BRCA1 and BRCA2 carriers combined and BRCA1 carriers and a reduced PBC risk in BRCA2 carriers.

Abstract P3-04-11: Longitudinal Changes of Contralateral Breast Mammographic Artificial Intelligence Algorithms Score in Ductal Carcinoma In Situ patient with Tamoxifen

Abstract Background Mammographic Artificial intelligence (AI) algorithms (Lunit insight MMG) draws attention as a diagnostic support tool for breast cancer detection. Lunit insight MMG provides a location suspected of breast cancer with a heatmap and a score reflecting the probability of the presence of suspicious areas. We investigated whether the Lunit insight MMG score is relevant for predicting the response to adjuvant tamoxifen. Methods Patients diagnosed with DCIS and underwent treatment at Seoul National University Hospital in 2010 were retrospectively enrolled. Clinical characteristics, tamoxifen use, survival data, and mammography images were extracted from the electronic medical records, and Lunit insight MMG scores were calculated retrospectively. We classified two groups according to tamoxifen treatment and compared the score change of contralateral breast from baseline to 5 years after surgery for DCIS. Change categories of Lunit insight MMG score included maintaining high risk, maintaining low risk, increasing from low risk to high risk, and decreasing from high risk to low risk. Results Of 100 patients, 50 (50%) had undergone tamoxifen treatment (group 1) and 50 (50%) had not (group 2). The median age of the patients was 48.4 years for group 1 and 51.5 years for group 2 (p=0.172). The median follow-up duration was 8.7 years for the whole cohort. Using Lunit insight MMG score, more patients in group 1 decreased in contralateral breast cancer (CBC) risk compared with group 2 (6.0% vs. 2.0%; P=.008). No patients in group 1 had an increase in CBC risk while 9 patients increased in group 2 (0% vs. 18.0%; P =.008). There was no ipsilateral breast cancer recurrence for the whole cohort, and two patients experienced contralateral invasive breast cancer in group 2. In two patients with CBC, the Lunit insight MMG score increased five years after surgery, one year and three years before the CBC diagnosis. Conclusions Longitudinal Changes of Mammographic AI algorithms Score may be a predictive surrogate marker for response to tamoxifen therapy in hormone receptor-positive DCIS. Citation Format: Changjin Lim, Eun Kyung Park, Hong-Kyu Kim, Eunhye Kang, Ji-Jung Jung, Hyunsu Yeoh, Jang-il Kim, Jung Whan Chun, Han-Byoel Lee, Hyeong-Gon Moon, Wonshik Han. Longitudinal Changes of Contralateral Breast Mammographic Artificial Intelligence Algorithms Score in Ductal Carcinoma In Situ patient with Tamoxifen [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P3-04-11.

Abstract P3-05-30: Survival after Development of Contralateral Breast Cancer

Abstract Purpose There are many studies reporting survival after development of contralateral breast cancer(CBC) but with inconsistent results. Also, many studies were based on European or North American population and few on Asian population. However, Korean breast cancer patients have different characteristics such as age distribution. Therefore, purpose of this study is to investigate whether development of CBC has influence on survival in Korean breast cancer population. Methods In this retrospective study, we included patients who were diagnosed with a first primary unilateral non-metastatic breast cancer at Asan Medical Center, Korea, between 1999-2013 followed through 2018. In this population, patients who delveloped CBC during the follow-up period were divided into the CBC cohort, and who did not into the non-CBC cohort. Survival of CBC cohort and non-CBC cohort was compared in the whole study population and in subgroup analysis by interval of CBC development, and breast cancer subtype. Results Over median follow-up of 107 months, 418 patients developed CBC out of 16,251 patients. Development of CBC did not influence overall survival or breast cancer-specific survival. In subgroup analysis by interval of CBC development, patients who developed CBC within one year after diagnosis of the first breast cancer had higher risk for overall death in CBC cohort (hazard ratio 2.58; 95% CI 1.28-5.18), and patients who developed CBC after one year showed no significant difference in survival compared with non-CBC cohort. In subgroup analysis by the subtype, patients with hormone receptor-positive/human epidermal growth factor receptor 2-negative subtype for the first breast cancer showed higher risk for overall death in CBC cohort (hazard ratio 1.88; 95% CI 1.14-3.10) whereas patients with triple negative subtype for the first breast cancer showed lower risk for overall survival in CBC cohort (hazard ratio 0.42; 95% CI 0.19-0.95). Conclusion Development of CBC in Korean breast cancer patients did not have significant impact on survival. However, development of CBC early after diagnosis of first breast or having certain subtype of breast cancer may have affect on survival. Such information can be important information when counseling patients who are considering contralateral prophylactic mastectomy. Citation Format: Hakyoung Kim, Hee Jeong Kim, Yoon Tae In, Seonok Kim, Sae Byul Lee, Jisun Kim, Il-Yong Chung, Beom Seok Ko, Jong Won Lee, Byung Ho Son, Sei Hyun Ahn. Survival after Development of Contralateral Breast Cancer [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P3-05-30.

Abstract P6-02-14: Contralateral breast cancer risk in patients with or without BRCA mutation

Abstract Background: Patients who carry mutated BRCA1 or BRCA2 genes have a significantly increased risk of breast cancer and developing contralateral breast cancer (CBC). In this study, we aimed to investigate the acceptance rate of BRCA1/2 testing in Korean breast cancer patients and to determine the risk of CBC in Korean patients with BRCA 1/2 germline mutations. Methods: This study included 13,109 patients with first primary breast cancer who were treated at Seoul National University Hospital from January 2005 to December 2018. These patients were divided into high-risk for BRCA1/2 mutation group and low-risk group. High risk patients were defined as those who were eligible for BRCA testing per Korean National Health Insurance Service. The high-risk group was further classified into three groups; BRCA1/2 mutation carrier, BRCA 1/2 non carrier and BRCA/12 untested. Results: Among the 4,446 high-risk patients, 962 (21.7%) patients underwent BRCA1/2 testing. The testing rate varied among different indications (47.8% of patients with a family history, 23.3% of patients under 40 years of age, and 13.0% of patients with triple negative breast cancer). The risk of the CBC in BRCA mutation group was higher than other groups (p value < 0.001). The 10-year cumulative risk of CBC was 11.0% BRCA1 mutation carrier and 7.4% for BRCA2 mutation carrier. In the BRCA1/2 non-carriers, the cumulative risk of CBC was 5.7%. Interestingly, the CBC risk for BRCA1/2 non-carriers significantly higher than BRCA1/2 untested group and the low-risk group (p < 0.001). When compared to the BRCA1/2 untested group, the relative risk for CBC was 6.7-fold increase for the BRCA1/2 mutation carrier group (95% CI = 3.65-12.22, p < 0.001), and 2.3-fold increase for the BRCA1/2 non-carriers group (95% CI = 1.44-3.83, p < 0.001). The relative risk for CBC in high-risk group also depended on subtype of breast cancer and family history. Hormone receptor negative breast cancer patients had a 1.5-fold (95% CI = 1.02-2.31, p = 0.04) increased risk of CBC and patients with one or more 1st degree relative with breast cancer had 2.4-fold increased risk (95% CI = 1.55-3.67, p < 0.001). Conclusion: About one out of five Korean breast cancer patients, who are eligible for the BRCA1/2 testing, undergo testing for BRCA1/2 germline mutations. We observed increased CBC risk not only for the BRCA1/2 mutation carriers but also for the BRCA1/2 non-carriers. At present, we are conducting multi-gene panel testing for the BRCA1/2 non-carriers to understand the mechanisms of the increased CBC risk. Citation Format: Eunhye Kang, Ji-Jung Jung, Hyunsu Yeoh, Changjin Lim, Jang-il Kim, Jung Whan Chun, Hong-Kyu Kim, Han-Byoel Lee, Wonshik Han, Hyeong-Gon Moon. Contralateral breast cancer risk in patients with or without BRCA mutation [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P6-02-14.

Abstract P5-04-04: Does reducing the frequency of regularly scheduled physical examinations affect recurrence detection in patients with early breast cancer?

Abstract Purpose: Follow-up care of patients with early breast cancer (EBC) usually includes routinely scheduled physical examinations. While ASCO guidelines recommend a physical exam every three to six months for the first three years, there is little evidence to support this schedule. Health care systems continue to be challenged to meet the future growth in demand from increasing numbers of diagnosed patients and long-term survivors, scarcity of health care workers, and the need to control health care costs. Despite recognition that new follow-up models are needed, there continues to be no generally accepted well follow-up strategy. We evaluated recurrence detection patterns of patients transferred into a single centre survivorship program that follows ASCO recommendations. Methods: Consecutive patients with EBC referred to the Wellness Beyond Cancer Program (WBCP) between February 1, 2013, and January 1, 2019, who had breast cancer recurrence, were reviewed. Descriptive analyses were used to present patients and disease characteristics stratified by type of recurrence and mode of cancer detection. Results: Of 206 recurrences, 135 were distant recurrences (65.5%), 41 were ipsilateral breast recurrences (19.9%), and 30 were contralateral new breast cancers (14.6%). Patient reported symptoms lead to the detection of the majority of distant recurrences (125/135, 92.6%). The most common symptoms of recurrence were bone pain (24.8%), dyspnea/cough (13.1%), abdominal pain (10.7%). Ipsilateral breast recurrences were both quite frequently detected by patients (22/41, 53.7) and by routine mammographic surveillance (17/21, 41.5%). Contralateral breast cancers were primarily detected by imaging 83.3% (25/30). Only 2/206 (1.14%) recurrences/new primaries were detected by a healthcare provider at routinely scheduled follow-up visits. There was a statistical difference in recurrence detection between image detected vs. self-detected in the following factors: grade 3 (26.5% vs 51%, p < 0.007), triple negative breast cancer (3.9% vs. 15.1%, p=0.03), and HER2 disease (18.4% vs. 9.8%, p= 0.04). Conclusions: Despite regularly scheduled in-person follow-up visits following ASCO guidelines, healthcare providers rarely detect recurrences. Our data suggests that 30,000 – 35, 000 follow-up visits were required for the healthcare providers to detect these 2 recurrences. This leads to further need for proper survivorship programs with patient and provider education, and concentration on targeted surveillance. Provided patients attend regular screening tests, our data points to less frequent in-person follow-up being associated with non-inferior breast cancer-related outcomes. Future prospective studies are required looking at different models of follow-up. SABCS Abstract Table Citation Format: Ana-Alicia Beltran-Bless, Bader I. Alshamsan, Mashari Alzahrani, John Hilton, Kelly-Anne Baines, Vicky Samuel, Gregory R. Pond, Lisa Vandermeer, Mark Clemons, Gail Larocque. Does reducing the frequency of regularly scheduled physical examinations affect recurrence detection in patients with early breast cancer? [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P5-04-04.

Abstract P2-02-03: Efficacy and Safety of the Addition of Internal Mammary Irradiation to Standard Adjuvant Radiation in Early-Stage Breast Cancer: A Systematic Review and Meta-analysis

Abstract Background: Adjuvant regional nodal irradiation together with whole breast or chest wall irradiation is considered standard of care in most node positive early breast cancer. Existing data on adding internal mammary irradiation (IMNI) to the regional nodal fields are inconsistent. The objective of this study was to conduct a meta-analysis to explore the efficacy and safety of adding IMNI to adjuvant radiotherapy in early-stage, high risk breast cancer. Methods: A search of PubMed and EMBASE identified randomized trials that investigated the addition of IMNI to standard adjuvant radiation in early-stage breast cancer. Hazard ratios (HRs) and 95% confidence intervals (CI) were extracted for overall survival (OS), breast cancer specific survival (BCSS), disease-free survival (DFS) and distant-metastasis free survival (DMFS). The odds ratios (ORs) for regional and loco-regional recurrence, non-breast cancer mortality, secondary non-breast cancer, contralateral breast cancer and cardiovascular morbidity and mortality were also extracted. These data where pooled in a meta-analysis using RevMan 5.4. Results: Analysis included 5 trials comprising 10,994 patients. Compared to the control group, IMNI was associated with a small, but statistically significant improvement in OS (HR=0.91, 95% 0.85-0.97, p=0.004), BCSS (HR=0.84, 95%0.77-0.92, p< 0.001), DFS (HR=0.89, 95% CI 0.82-0.98, p= 0.01) and DMFS (HR=0.89, 95% 0.81-0.98, p=0.02). IMNI was also associated with reduced odds for regional (OR=0.58, 95% 0.44-0.75, p< 0.001) and loco-regional recurrence (OR=0.85, 95% CI 0.72-1.00, p=0.04). Subgroup analyses for OS by tumor location (medial/central vs. lateral) and by nodal burden showed similar benefit is all subgroups. The odds for cardiotoxicity were higher, but did not reach statistical significance (OR=1.23, 95% 0.99-1.53, p=0.07). There was no association with cardiovascular mortality (OR=1.00, 95% 0.69-1.46, p=1.00). There were also comparable odds for non-breast cancer mortality (OR=1.05, 95% 0.79-1.41, p=0.74), secondary cancer (OR=0.95, 95% 0.82-1.10, p=0.51) and contra-lateral breast cancer (OR=1.07, 95% 0.77-1.51, p=0.68). Conclusions: Compared to the control group the addition of IMNI in high-risk patients is associated with a statistically significant improvement in survival, albeit with a magnitude of questionable clinical meaningfulness. Non-significant association with increased cardiovascular toxicity requires further study in longer-term studies. Citation Format: Yasmin Korzets, Dina Levitas, Ahuva Grubstein, Ben W Corn, Eitan Amir, Hadar Goldvaser. Efficacy and Safety of the Addition of Internal Mammary Irradiation to Standard Adjuvant Radiation in Early-Stage Breast Cancer: A Systematic Review and Meta-analysis [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P2-02-03.

Abstract P5-03-01: Long-term oncologic outcome of unselected triple-negative breast cancer patients according to BRCA1/2 mutations: a comprehensive single institution study

Abstract Background Triple-negative breast cancer (TNBC) is known to have a higher risk of early recurrence and relatively low risk of late recurrence compared to luminal type breast cancer. Among all subtypes of breast cancer, TNBC is more likely to have BRCA1/2 germline mutation which showed prevalence rate from about 10% to 20% in previous reports. To date, there are only few studies about the effect of BRCA1/2 mutations on the long-term oncologic prognosis in TNBC patients. We analyzed long-term oncologic outcome in unselected TNBC patients according to BRCA1/2 mutations in a comprehensive single institution. Methods Among 11,994 patients who underwent primary breast cancer surgery at Samsung Medical Center (SMC) between June 2008 and January 2016, 1,628 (13.6%) were TNBC patients. Of those, patients with inadequate and unavailable samples at SMC biobank and patients with follow-up duration less than 12 months and who had distant metastasis at presentation were excluded from the study, and 953 patients were enrolled. A retrospective study was conducted and BRCA1/2 genetic testing was done with SMC biobank samples through Next Generation Sequencing (NGS). Results Among 953 unselected TNBC patients, 122 patients (12.8%) had BRCA1/2 mutations: 91 (9.5%) were in BRCA1, and 32 (3.4%) were in BRCA2. One patient had both BRCA1/2 mutations. BRCA1/2 carriers were more likely to have personal history of ovarian cancer (9.0% vs. 0.5%, p < 0.0001), family history of breast cancer and/or ovarian cancer (40.2% vs. 9.4%, p < 0.0001), bilateral breast cancer (4.9% vs. 1.2%, p = 0.0105), and higher nuclear grade (86.0% vs. 74.0%, p = 0.0250). The median follow-up duration was 80.9 months. There were no significant differences in disease-free survival (DFS), distant metastasis-free survival (DMFS), overall survival (OS), and breast cancer-specific survival (BCSS) (p = 0.375, 0.268, 0.413, and 0.133, respectively) between BRCA1/2 carriers and non-carriers. However, BRCA1/2 carriers showed significantly worse contralateral breast cancer (CBC)-free survival than non-carriers (p < 0.0001). Sixty and 120-months cumulative recurrence rate were 18.5% and 31.2% for BRCA1/2 carriers versus 19.3% and 22.7% for non-carriers (p = 0.834 and 0.136, respectively). However, cumulative recurrence rate at 150 months showed absolute but not statistically significant difference between BRCA1/2 carriers and non-carriers (36.2% versus 23.5%, p = 0.080). Cumulative CBC recurrence rate on 60, 120- and 150-months estimates were 6.7%, 18.7% and 25.5% for BRCA1/2 carriers versus 1.1%, 2.7% and 5.2% for non-carriers which showed statistically meaningful difference (p = 0.025, 0.006 and 0.018, respectively). Sixty months, 120- and 150-months cumulative expire rate were 11.2%, 15.6% and 27.7% for BRCA1/2 carriers versus 14.3%, 20.7% and 20.7% for non-carriers (p = 0.319, 0.202 and 0.549, respectively). Discussion In this unselected cohort of patients with TNBC, we found 12.8% (122 patients among 953) prevalence of BRCA1/2 mutations. The median follow-up duration was 80.9 months. There was no significant difference in DFS, DMFS, OS and BCSS by BRCA1/2 mutation status in long-term follow up. However, BRCA1/2 carriers showed significantly worse CBC recurrence rate at 60, 120- and 150- months. And also, BRCA1/2 carriers had 12.7% higher risk of recurrence than non-carriers at 150 months, which was not statistically meaningful but showed absolute difference. Among patients with CBC recurrence, 41.3% (12 patients among 29) were BRCA1 carriers, over 85% had TNBC type of recurred CBC and approximately 80% underwent chemotherapy. In conclusion, we demonstrated that CBC recurrence risk is relatively high in TNBC patients with BRCA1 mutation and showed high chance to receive chemotherapy. Therefore, long-term follow up and appropriate genetic counseling, risk assessment should be done properly for BRCA1/2 mutation carriers in TNBC patients. Citation Format: Soo Yeon Chung, Jai Min Ryu, You Jin Jung, Yeon Jin Kim, Hye Jin Kim, Seok Jin Nam, Seok Won Kim, Jonghan Yu, Byung Joo Chae, Jeong Eon Lee, Se Kyung Lee, Sung-Won Kim, Eun Young Kim. Long-term oncologic outcome of unselected triple-negative breast cancer patients according to BRCA1/2 mutations: a comprehensive single institution study [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P5-03-01.