Diagnosis Of Primary Breast Cancer Research Articles

Characterizing access for oral oncolytics used to treat breast cancer at an academic medical center.

116 Background: Everolimus, CDK 4/6, PIK3CA, Her2 tyrosine kinase, and PARP inhibitors are commonly used oral oncolytic agents for breast cancer patients. However, oral oncolytics are tiered differently for insurance cost coverage than IV therapies. We characterized the financial toxicity associated with breast cancer oral oncolytics, investigated the prevalence of financial assistance mechanisms utilized, and explored the association of these mechanisms with timing of treatment initiation in adult breast cancer patients. Methods: Patients 18 years or older with a primary breast cancer diagnosis who received care at the outpatient breast cancer clinic and were prescribed an oral oncolytic by a Michigan Medicine provider were included. Using the electronic medical record, we identified initial prescriptions for everolimus, CDK 4/6 inhibitors (palbociclib, ribociclib, abemaciclib), PIK3CA inhibitor (alpelisib), HER2 tyrosine kinase inhibitors (lapatinib, neratinib, tucatinib), and PARP inhibitors (olaparib, talazoparib) dated between January 1, 2014 and November 30, 2022. Patient demographics, adjuvant versus metastatic status, insurance coverage, monthly out-of-pocket costs, financial assistance obtained, prescribed date, planned medication start date, pill-to-mouth date, duration of treatment and reason for treatment discontinuation were collected. Results: There were 418 unique patients in our final cohort. Almost one third of all prescriptions were filled with financial assistance (n=126, 31.2%). The three most common assistance mechanisms were copay cards (n=55, 43.6%), grants (n=34, 26.9%) and patient assistance programs (n=31, 24.6%). For monthly out-of-pocket costs before any financial assistance was obtained, the three most common cost groups were $0-$15 (n=155, 36%), $15-$100 (n=101, 23.7%) and >$500 (n=91, 21%). Among the 48 prescriptions that were never filled, almost one third were due to prohibitive cost (n=15, 28.3%). For insurance coverage, the three most common types were commercial (n=224, 54%), Medicare Part D (n=108, 26%), and Medicaid (n=57, 14%). The median number of days treatment was delayed was 10 days (range 0-495 days). Insurance approval/denial delays accounted for 33.9% of delays (n=120). Conclusions: One third of breast cancer oral oncolytic prescriptions were filled with financial assistance. In the instances in which patients were not able to receive timely treatment for their cancer, one out of three times it was due to insurance delay.

Universal Genetic Testing for Newly Diagnosed Invasive Breast Cancer

Between 5% and 10% of breast cancer cases are associated with an inherited germline pathogenic or likely pathogenic variant (GPV) in a breast cancer susceptibility gene (BCSG), which could alter local and systemic therapy recommendations. Traditional genetic testing criteria misses a proportion of these cases. To evaluate the prevalence and clinicopathological associations of GPVs in 2 groups of BCSGs among an ethnically diverse cohort of women with newly diagnosed breast cancer. This cross-sectional study, conducted at 3 Montreal hospitals between September 2019 and April 2022, offered universal genetic counseling and testing to all women with a first diagnosis of invasive breast cancer. Women were offered an obligatory primary panel of BRCA1, BRCA2, and PALB2 (B1B2P2) and an optional secondary panel of 14 additional BCSGs. Eligible participants were women 18 years of age or older who received a diagnosis of a first primary invasive breast cancer not more than 6 months before the time of referral to the study. Data were analyzed from November 2023 to June 2024. Of 1017 referred patients, 805 were eligible and offered genetic counseling and testing, and 729 of those 805 (90.6%) consented to be tested. The median age at breast cancer diagnosis was 53 years (range, 23-91 years), and 65.4% were White and of European ancestry. Fifty-four GPVs were identified in 53 patients (7.3%), including 39 patients (5.3%) with B1B2P2 and 15 patients (2.1%) with 6 of the 14 secondary panel BCSGs (ATM, BARD1, BRIP1, CHEK2, RAD51D, and STK11). On multivariable analysis, clinical factors independently associated with B1B2P2-positive status included being younger than 40 years of age at diagnosis (odds ratio [OR], 6.83; 95% CI, 2.22-20.90), triple-negative breast cancer (OR, 3.19; 95% CI, 1.20-8.43), high grade disease (OR, 1.68; 95% CI, 1.05-2.70), and family history of ovarian cancer (OR, 9.75; 95% CI, 2.65-35.85). Of 39 B1B2P2-positive patients, 13 (33.3%) were eligible for poly(adenosine diphosphate-ribose) polymerase (PARP) inhibitors. In this cross-sectional universal genetic testing study of women with newly diagnosed invasive breast cancer, the prevalence of GPVs was 7.3%, with 5.3% of patients testing positive for B1B2P2. Among B1B2P2-women women, one-third were eligible for PARP inhibitors.

A survey of women diagnosed with breast cancer experiencing oncology treatment-induced hot flushes: identification of specific characteristics as predictors of hot flush occurrence, frequency, and severity.

More women diagnosed with breast cancer (BC) are living with oncology treatment-induced hot flushes (HFs). This Australian-based survey explores why some women experience more severe or ongoing HF and whether specific population characteristics are predictive of HF occurrence, frequency, and/or severity. A non-probabilistic anonymous survey distributed online (Register4) and two Australian hospitals collected demographic and clinical information. Eligibility was consenting Australian-based women, 18 years and over, with a primary BC diagnosis. Analysis included linear and logistic regression models. A total of 324 survey responses were analyzed. Chemotherapy and hormone therapy were each associated with HF occurrence (aOR = 2.92, 95% CI [1.27, 6.70], p = 0.01; and aOR = 7.50, 95% CI [3.02, 18.62], p < 0.001) and in combination (aOR = 5.98, 95% CI [2.61, 13.69], p < 0.001). Increased self-reported anxiety at BC diagnosis was significantly associated with HF frequency and severity scores (aCO = 0.71, 95% CI [0.31, 1.12], p = 0.001; and aCO = 0.44, 95% CI [0.33, 0.55], p < 0.001). Postmenopausal women had significantly lower HF severity and frequency scores than premenopausal women (aCO = -0.93, 95% CI [-1.62, -0.25], p = 0.008; and aCO = -2.62, 95% CI [-5.14, -0.11], p = 0.041). Women with BC receiving chemotherapy and/or hormone therapy and premenopausal or experiencing elevated anxiety and/or stress will likely experience more severe oncology treatment-related HFs. HFs continue across the BC treatment trajectory with women >5-year survivorship still reporting life impacts, with premenopausal women at the time ofBCdiagnosis at higher risk of experiencing severe and more frequentoncology treatment-induced HFs than postmenopausal women. Women at high risk require information on methods to moderate HF potential life impacts and maintain treatment compliance.

Effect of timing of recurrence on outcomes in patients with metastatic breast cancer treated with CDK4/6 inhibitors.

e13067 Background: CDK4/6 inhibitors (CDKi) + endocrine therapy (ET) comprise the standard 1st line treatment for ER+ HER2- metastatic breast cancer (MBC). However, there is a gap in understanding how timing of MBC recurrence affects clinical outcomes on CDKi. We conducted a study to compare clinical outcomes of MBC patients on CDKi based on timing of MBC recurrence. Methods: This retrospective study enrolled ER+ HER2- MBC patients diagnosed from Jan 2015 to Jan 2023, who received CDKi + ET as 1st line treatment for MBC. Patients were categorized as de novo MBC (dMBC), if they had 1. Stage 4 disease at initial diagnosis or 2. MBC diagnosed &lt; 6 months of the primary breast cancer (PBC) diagnosis and before starting any systemic treatment for PBC. Patients with distant recurrence occurring &lt; 5 years, 5-10 years, and &gt;10 years from PBC were categorized as early, intermediate, and late MBCs (eMBC, iMBC, laMBC). Endpoints were Progression-Free Survival (PFS) and Overall Survival (OS) from MBC diagnosis. Baseline variables were compared using t-tests (continuous) and Chi-square tests (categorical). Endpoint analyses were conducted using Kaplan-Meier method and compared using Log rank test. Multivariate analyses were performed using Cox models. Results: Out of 280 patients enrolled, 67 were dMBC, 75 eMBC, 56 iMBC, and 82 laMBC. The laMBC group had a higher mean age (years) compared to other groups (71 vs. 62 in dMBC+ eMBC + iMBC, p&lt;0.001). 64.5% of laMBC had visceral disease compared to 50.5% of dMBC + eMBC + iMBC (p=0.031). 65.7% of dMBC patients were treated with palbociclib compared to 80.8% of eMBC + iMBC + laMBC (p=0.010). Higher % of eMBC were PR- vs other cohorts (41.3 vs 23.9 dMBC + iMBC + laMBC, p&lt;0.001). Among the 3 non dMBC groups, prior ET sensitivity (no recurrence for 2 years on adjuvant ET) was lower in eMBC (45.3%) compared to iMBC + laMBC (81.9%, p&lt;0.001). 61.3% of eMBC patients were on adjuvant ET at recurrence compared to 17.4% of iMBC + laMBC (p&lt;0.001). Other variables were similar. Table shows unadjusted endpoint analyses. In multivariate analyses, the risk of PFS events were not significantly different among cohorts (age&lt;=65, ECOG performance status (PS) &gt;=2 and PR- were independently associated with shorter PFS); risk of death was higher in eMBC vs laMBC (HR 1.73, p=0.047). Conclusions: In this retrospective study of ER+ HER2- MBC patients treated with 1st line CDKi + ET, timing of MBC recurrence was not associated with PFS differences after adjusting for other variables. However, patients with MBC recurring &lt; 5 years of PBC had the higher likelihood of death compared to those recurring &gt;10 years of PBC. [Table: see text]

Abstract PO3-11-10: Second primary non-breast cancers in young breast cancer survivors

Abstract Adolescent and young adults (AYAs) (15-39 years) have a heightened risk of developing a second primary malignancy due to extended periods of survivorship, higher incidence of germline cancer predisposing variants, and increased susceptibility to treatment-induced malignancies. Research on survivors of specific AYA cancer types, including breast cancer (BC) survivors, is limited. Among BC survivors, while much survivorship research focuses on risk of locoregional recurrence or contralateral BC, little is known about overall risk, and risk factors, of developing second non-breast primaries. This prospective cohort study examined women diagnosed with BC from 2006-2016 at age ≤40 years enrolled in the Young Women’s BC Study (YWS) (N=1297). Women were excluded from the analytic cohort if initially diagnosed with Stage IV breast cancer (N=64). To enable investigation of how BC treatments may impact second primary risk, women were also excluded if they reported another cancer before primary BC diagnosis (N=3). Patient characteristics, treatment information, and clinical events were collected via serial surveys. Tumor characteristics and detailed treatment data were obtained from medical record review. Five- and 10-year risk of second non-breast primary was estimated via the cumulative incidence function after applying the Fine-Gray competing risks model with time starting at primary BC diagnosis. Death, metastasis, or diagnosis with a second primary BC were considered as competing events. Univariate and multivariate Fine-Gray sub-distribution models were used to estimate sub-distribution hazard ratios (sHRs) and 95% confidence intervals (CI) for second non-breast primary cancer risk. Risk factors considered included age, race, body mass index, smoking, alcohol use, income, family history of cancer, germline pathogenic variant (PV) carrier status, tumor stage, grade, and ER status, primary surgery type, and receipt of radiation, chemotherapy, or endocrine therapy (yes/no). Multivariate models tested individual associations with additional adjustment for radiation therapy and PV carrier status, as both are consistently associated with second primary in the literature. Over a median follow-up of 10.1 years (inter-quartile range (IQR) =7.9-12.1 y), 47 patients (4%) developed a second non-breast primary cancer. Median age at second non-breast primary was 43 years (IQR=39-46), and median time between primary BC and second non-breast primary was 7.3 years (IQR=4.1-9.3). Second primary types included melanoma (n=10), thyroid (n=10), ovarian (n=4), sarcoma (n=4), uterine (n=3), rectal (n=3), bladder (n=2), cervical (n=2), head and neck (n=2), lung (n=2), lymphoma (n=2), pancreatic (n=2), and kidney (n=1). During the study, 22 patients (2%) developed a second primary BC, 167 (19%) developed metastasis, and 15 (1%) died from causes other than BC. Among the patients who developed a second primary BC, two later developed another non-breast cancer (ovarian and brain cancer). When incorporating competing risks, five and 10-year cumulative incidence of second non-breast primary was 1.4% and 3.2%, respectively. No patient or treatment factors were statistically significantly associated with second non-breast primary in univariate or multivariate models, including radiation and PV carrier status. In this population of young BC survivors, 10-year cumulative incidence of second non-breast primary cancer was 3.2%, with the most common second cancers being melanoma and thyroid cancer. Incidence rates of all second primary cancer types in this cohort were higher than population-based incidence rates for healthy women under 50 years of age, highlighting the importance of long-term surveillance for other cancer events in this young population. While risk of second non-breast primary was not associated with primary BC treatment in this study, cases were limited, and the follow-up interval was relatively short. Citation Format: Bessie Zhang, Kristen Brantley, Shoshana Rosenberg, Gregory Kirkner, Laura Collins, Kathryn Ruddy, Rulla Tamimi, Lidia Schapira, Virginia Borges, Ellen Warner, Steven Come, Eric Winer, Ann Partridge. Second primary non-breast cancers in young breast cancer survivors [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 PO3-11-10.

Abstract PO3-27-07: Age at diagnosis and the food environment are associated with postdiagnosis weight gain among Black American breast cancer survivors in Maryland

Abstract Background: Weight management is now included in the American Cancer Society/American Society of Clinical Oncology Breast Cancer Survivorship Care Guidelines due to its clinical impact on breast cancer (BC) survivorship outcomes. While numerous individual-level risk factors for weight gain after BC diagnosis have been identified, such as younger age at diagnosis, cancer stage, and cancer treatments (chemotherapy), there are limited data on the impact of neighborhood-level factors associated with weight change postdiagnosis among Black BC survivors. Methods: Utilizing social media recruitment strategies and survivor networks, we recruited 100 Black female BC survivors to complete an online survey, including demographic, clinical characteristics, and lifestyle factors, between January 5, 2022, and August 18, 2022. To capture the food environment, we utilized the 2023 Food Environment Index County Health Rankings, which accounts for access to healthy foods due to proximity and income (considering the distance an individual lives from a grocery store or supermarket, locations for health food purchases in most communities, and the inability to access healthy food because of cost barriers). The index ranges from 0 (worst) to 10 (best). Our outcome of postdiagnosis weight gain was calculated as percent weight change from time at diagnosis to time of survey, calculated as ([weight at survey – weight at diagnosis]/weight at diagnosis) × 100. Participants were grouped into mutually exclusive categories of stable weight (within ± 3%) or weight loss (≤-3%) compared to weight gain (≥ 3%). Adjusted odds ratios (aORs) and 95% confidence intervals (CI) were calculated for the associations between clinical factors, county-level food environment index, and postdiagnosis weight gain. Results: The average ages at time of survey and at primary BC diagnosis were 58.6 years (standard deviation [SD]= 10.1) and 49.1 years (SD=10.2), respectively. Most women (70%) were diagnosed with invasive BC and only 22% were currently undergoing treatment at the time of the survey. While only 7% reported being obese at the time of BC diagnosis, 54% reported being obese at the time of survey which was on average 9 years post-BC diagnosis; and while 61 women had weight loss or stable weight, 34 women experienced weight gain postdiagnosis. Among the 95 women included in multivariable models who reported weight and height measurements for calculating weight change, women ≥50 years of age at BC diagnosis (versus &amp;lt; 50 years) were 3.43 times more likely to gain weight after diagnosis (95% CI 1.13-11.50). Women living in counties with a Food Environment Index ≥8.8 (median cut-point compared to &amp;lt; 8.8) were significantly less likely to experience weight gain (aOR 0.11; 95% CI 0.01-0.90). Stage and BC treatments were not significantly associated with weight gain. Conclusions: Our study findings demonstrate the importance of evaluating the food environment during BC survivorship and longitudinal monitoring of weight postdiagnosis to mitigate weight gain among Black BC survivors. Our findings will be used to inform a larger prospective study and future interventions among this population. Citation Format: Avonne Connor, Katherine Ho, Kate Dibble, Kala Visvanathan. Age at diagnosis and the food environment are associated with postdiagnosis weight gain among Black American breast cancer survivors in Maryland [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 PO3-27-07.

Abstract PO5-06-01: Loss of hormone receptor expression in breast cancer is associated with increased brain tropism and accelerated progression of leptomeningeal disease

Abstract The four breast cancer subtypes—luminal A, luminal B, HER2-overexpressing, and triple-negative breast cancer (TNBC) – are classified based on gene expression profiles of hormone receptors (HRs) (estrogen receptor (ER) and progesterone receptor (PR)) and human epidermal growth factor receptor 2 (HER2/ERBB2). Negative hormone receptor status is known to be associated with more aggressive breast cancer. Compared to other breast cancer subtypes, the HR-negative TNBC and HER2-overexpressing subtypes are characterized by high rates of recurrence and a notable increase in brain metastases and in particular, leptomeningeal disease (LMD). LMD – the most aggressive form of central nervous system (CNS) metastasis, in which cancer cells infiltrate leptomeninges of the brain and spine – carries a dismal prognosis due to a rapid progression, poor detection, and no effective treatment. Several studies that investigated the link between HR status and LMD suggest that HR-negative breast cancers have a shorter time to LMD diagnosis. This shortened timeline is consistent with higher migratory capabilities reported for TNBC and HER2 breast cancer cells. However, as it is known that breast cancers exhibit subtype-specific metastatic tropism (i.e., luminal subtypes tend to metastasize to bone and liver, while TNBCs metastasize to the CNS), the longer time between primary breast cancer diagnosis and LMD diagnosis for HR-positive breast cancers may also reflect a longer metastatic route that first includes a non-CNS location. In this study, we performed a retrospective analysis on 141 breast cancer patients with LMD treated at Stanford Hospital between 2008-2020. The Stanford LMD cohort was analyzed using linear regression analysis, Cox regression analysis, and Chi-squared analysis. HR status was recorded (when available) for local recurrences and distant metastases, and was included in our regression models as a time-dependent HR covariate. We tested if: (1) HR-negative breast cancers had shorter time between primary and LMD diagnosis as well as worse survival after LMD diagnosis versus HR-positive breast cancers, and if (2) HR loss (i.e., HR status changing from positive to negative) increased likelihood of the metastasis to CNS. In agreement with published studies, the Stanford LMD cohort showed that HR-negative cancers had shorter time to development of LMD (p = 0.0004 for ER, p = 0.0001 for PR) and increased mortality following LMD (p = 0.010 for ER, p = 0.009 for PR). We found that HR-negative status at primary breast cancer diagnosis increased risk of first metastasis to CNS versus non-CNS locations (p = 0.021 for ER, p = 0.043 for PR). HR status switch (also known as hormone discordance) between primary diagnosis and metastasis occurred in 15% of patients in Stanford cohort, consistent with other studies. Importantly, accounting for HR status switch strengthened the association between HR-negative status and the risk of CNS metastasis [Hazard Ratio = 2.506 (1.395 - 4.500) for “baseline ER status” versus Hazard Ratio = 3.509 (1.890 - 6.515) for “time-dependent ER status”, Hazard Ratio = 2.420 (1.310 - 4.471) for “baseline PR status” versus Hazard Ratio = 3.407 (1.815 - 6.395) for “time-dependent PR status”]. In conclusion, HR-negative status was associated with shorter time to development of LMD, higher CNS tropism, and shorter survival following LMD diagnosis. Taking into consideration hormone discordance between the primary tumor and metastatic sites strengthened this association. Our results suggest a potential value in testing HR status at all recurrences and advanced CNS monitoring following HR loss. Citation Format: Sophia Pribus, Maxine C. Umeh-Garcia, Bo Gu, Bryanna Godfrey, Summer Han, Sophia Chernikova, Melanie Hayden Gephart. Loss of hormone receptor expression in breast cancer is associated with increased brain tropism and accelerated progression of leptomeningeal disease [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 PO5-06-01.

Mammographic features at primary breast cancer diagnosis in relation to recurrence-free survival

PurposeThe number of women living with breast cancer (BC) is increasing, and the efficacy of surveillance programs after BC treatment is essential. Identification of links between mammographic features and recurrence could help design follow up strategies, which may lead to earlier detection of recurrence. The aim of this study was to analyze associations between mammographic features at diagnosis and their potential association with recurrence-free survival (RFS). MethodsWomen with invasive BC in the prospective Malmö Diet and Cancer Study (n = 1116, 1991–2014) were assessed for locoregional and distant recurrences, with a median follow-up of 10.15 years. Of these, 34 women were excluded due to metastatic disease at diagnosis or missing recurrence data. Mammographic features (breast density [BI-RADS and clinical routine], tumor appearance, mode of detection) and tumor characteristics (tumor size, axillary lymph node involvement, histological grade) at diagnosis were registered. Associations were analyzed using Cox regression, yielding hazard ratios (HR) with 95 % confidence intervals (CI). ResultsOf the 1082 women, 265 (24.4 %) had recurrent disease. There was an association between high mammographic breast density at diagnosis and impaired RFS (adjusted HR 1.32 (0.98–1.79). In analyses limited to screen-detected BC, this association was stronger (adjusted HR 2.12 (1.35–3.32). There was no association between mammographic tumor appearance and recurrence. ConclusionRFS was impaired in women with high breast density compared to those with low density, especially among women with screen-detected BC. This study may lead to insights on mammographic features preceding BC recurrence, which could be used to tailor follow up strategies.

Second Primary Breast Cancer in Young Breast Cancer Survivors

Among women diagnosed with primary breast cancer (BC) at or younger than age 40 years, prior data suggest that their risk of a second primary BC (SPBC) is higher than that of women who are older when they develop a first primary BC. To estimate cumulative incidence and characterize risk factors of SPBC among young patients with BC. Participants were enrolled in the Young Women's Breast Cancer Study, a prospective study of 1297 women aged 40 years or younger who were diagnosed with stage 0 to III BC from August 2006 to June 2015. Demographic, genetic testing, treatment, and outcome data were collected by patient surveys and medical record review. A time-to-event analysis was used to account for competing risks when determining cumulative incidence of SPBC, and Fine-Gray subdistribution hazard models were used to evaluate associations between clinical factors and SPBC risk. Data were analyzed from January to May 2023. The 5- and 10- year cumulative incidence of SPBC. In all, 685 women with stage 0 to III BC (mean [SD] age at primary BC diagnosis, 36 [4] years) who underwent unilateral mastectomy or lumpectomy as the primary surgery for BC were included in the analysis. Over a median (IQR) follow-up of 10.0 (7.4-12.1) years, 17 patients (2.5%) developed an SPBC; 2 of these patients had cancer in the ipsilateral breast after lumpectomy. The median (IQR) time from primary BC diagnosis to SPBC was 4.2 (3.3-5.6) years. Among 577 women who underwent genetic testing, the 10-year risk of SPBC was 2.2% for women who did not carry a pathogenic variant (12 of 544) and 8.9% for carriers of a pathogenic variant (3 of 33). In multivariate analyses, the risk of SPBC was higher among PV carriers vs noncarriers (subdistribution hazard ratio [sHR], 5.27; 95% CI, 1.43-19.43) and women with primary in situ BC vs invasive BC (sHR, 5.61; 95% CI, 1.52-20.70). Findings of this cohort study suggest that young BC survivors without a germline pathogenic variant have a low risk of developing a SPBC in the first 10 years after diagnosis. Findings from germline genetic testing may inform treatment decision-making and follow-up care considerations in this population.

Head-to-head comparison of cone-beam breast computed tomography and mammography in the diagnosis of primary breast cancer: A systematic review and meta-analysis

IntroductionTo compare the diagnostic performance of cone-beam breast computed tomography (CBBCT) and mammography (MG) in primary breast cancer. MethodsPubMed, Embase, Web of Science, China National Knowledge Infrastructure, WanFang DATA, and China Science and Technology Journal databases were searched comprehensively from inception to March 2023. Sensitivity and specificity were calculated using bivariate random-effects models, and a summary receiver operating characteristic (SROC) curve was constructed. Bivariate I2 statistics and meta-regression analyses were also performed. The differences in diagnostic performance between CBBCT and MG were analysed using Z-test statistics. Clinical utility was explored using Fagan’s nomogram, and quality assessment was conducted utilising the Quality Assessment of Diagnostic Accuracy Studies-2 checklist. ResultsThe summary sensitivity and specificity for CBBCT in diagnosing primary breast cancer were 0.92 (95 % CI: 0.87–0.94) and 0.79 (95 % CI: 0.71–0.85), respectively, and the area under the curve (AUC) of the SROC was 0.93 (95 % CI: 0.90–0.95). For MG, the summary sensitivity and specificity were 0.77 (95 % CI: 0.69–0.83) and 0.75 (95 % CI: 0.66–0.82), respectively, with an AUC of 0.83 (95 % CI: 0.80–0.86). The Z-test revealed that the summary sensitivity of CBBCT was significantly higher than that of MG (P < 0.001). Additionally, the summary AUC of CBBCT was significantly higher than that of MG (P < 0.001). ConclusionThe diagnostic performance of CBBCT for primary breast cancer was better than that of MG. However, the results of both the CBBCT and MG are based on studies with small sample sizes. Further studies with larger sample sizes and more comprehensive designs are required to address this issue.

Residential surrounding greenness is not associated with incident breast cancer in young women in Ontario, Canada

ObjectivesEnvironmental exposures play an important role in the development of breast cancer. The incidence of breast cancer is increasing in young women, and its etiology differs from that of older women. Epidemiological studies have provided mixed evidence about whether proximity to urban greenness reduces the risk of breast cancer, but few studies have evaluated this risk in younger women.MethodsWe investigated associations between residentially-based measures of greenness and breast cancer among participants of the Ontario Environmental Health Study (OEHS). The OEHS was a case–control study of Ontario women, 18–45 years of age, who provided questionnaire data between 2013 and 2015. The study included 465 cases diagnosed with a pathologically confirmed primary diagnosis of breast cancer, and 242 population-based controls. Residentially-based measures of greenness, the Normalized Difference Vegetation Index (NDVI) and tree coverage percentage, at 100-, 250-, 500-, and 1,000-m buffers, were assigned to the residential histories of the women. Odds ratios and their 95% confidence intervals (CIs) were estimated using logistic regression, adjusted for potential confounders including traffic-related air pollution [nitrogen dioxide (NO2)].ResultsWe found no evidence that an increase in NDVI or tree coverage were significantly associated with breast cancer. The adjusted odds ratio of breast cancer in relation to an interquartile range increase (IQR) in the NDVI (500-m buffer) was 0.86 (95% CI = 0.59–1.13). Similarly, the odds ratio of breast cancer among those in the highest quartile of tree coverage (500-m buffer) relative to the lowest was 1.11 (95% CI = 0.59–2.07). Risk estimates for both measures of greenness did not vary substantially across different buffer distances. Exposure to NO2 was an important confounder in these associations.ConclusionsOur findings do not support the hypothesis that residential greenness reduces the risk of breast cancer among young women, while highlighting the importance of adjusting for air pollution.

Infographics on signs and symptoms of metastatic (secondary) breast cancer can empower women with a breast cancer diagnosis.

We investigated the usefulness of a metastatic (secondary) breast cancer Infographics designed to enhance knowledge about symptoms of metastatic breast cancer in women diagnosed with breast cancer. Women with a primary or metastatic diagnosis of breast cancer who had not been in receipt of the Infographics previously, were sent the Infographics and asked to complete a questionnaire measuring their views of the usefulness of the Infographics in a number of domains. They were also asked to complete questionnaires on, anxiety and depression, coping, emotion regulation strategies and perceived cognitive functioning. Results showed that women advocated the use of the Infographics in medical and health care settings, as well as its ability in equipping themwith the relevant knowledge on signs of recurrence, its benefits in empowering control and reducing fears and uncertainties regarding metastatic breast cancer. Exploratory analysis showed that individual differences in trait vulnerability to anxiety and in emotion regulation strategies modulated women's responses suggesting the use of tailored approaches in the communication of the Infographics with patients. Our results point to the overall benefits of the Infographics in a number of domains. Implications for applications in healthcare settings are discussed.

A Case of Male Breast Cancer and a Literature Review

Background: Breast cancer in men, similar to that in women, originates in the mammary gland epithelium (ducts), and although less common than in women, its incidence has increased in recent decades, accompanied by significant advances in understanding the disease as a distinct entity. It shares important similarities with its female counterpart, with significant progress in diagnosis and treatment. Case presentation: In this report, we describe the clinical and imagenological characteristics of a 64-year-old man with metastatic adenocarcinoma to the skin. The patient presented with an ulcerative lesion on the right hemithorax, along the mid-clavicular line and anterior axillary line at the fifth intercostal space. The lesion had a soft, necrotic appearance, was prone to bleeding, and was referred by the patient as "resulting from trauma" a year ago, with progressive expansion and deepening, despite antibiotic use and cleansing of the wound. It invaded the surrounding skin, which appeared desquamated, erythematous with neovascularization, friable to the touch prone to bleeding with difficulty to achieve hemostasis, and multiple brownish nodular satellite lesions, with no other associated symptoms. A thoracic CT scan performed in the emergency department revealed a bilateral pleural effusion, predominantly on the right side, occupying 50% of the right lung space, along with an osteolytic lesion at the level of the manubrium of the sternum. A follow-up thoracic CT scan showed a pleural effusion occupying 80% of the right lung space, with a minor pneumothorax. The placement of an endopleural chest tube on the right side resulted in the extraction of 1800 ml of serosanguineous fluid, and pleural fluid culture did not reveal microorganisms or tumor cells, making the diagnosis of pulmonary adenocarcinoma less likely. A biopsy of the surrounding tissue yielded an invasive, poorly differentiated adenocarcinoma. Immunohistochemical staining was positive for estrogen and progesterone receptors, CK19, and negative for CK7, CK20, leading to the primary diagnosis of breast cancer based on clinical presentation and lesion location. Conclusions: Breast cancer in men, while sharing similarities with its female counterpart, presents its own unique characteristics. The identification of these factors and education about the significance of this condition, along with the discovery of specific biomarkers and targeted therapies, have the potential to significantly improve the prognosis of male patients in the future.

Upright patient positioning for gantry-free breast radiotherapy: feasibility tests using a robotic chair and specialised bras.

For external beam radiotherapy using photons or particles, upright patient positioning on a rotating, robotic chair (a gantry-less system) could offer substantial cost savings. In this study, we considered the feasibility of upright breast radiotherapy using a robotic radiotherapy chair, for (i) a cohort of 9 patients who received conventional supine radiotherapy using photons for a diagnosis of primary breast cancer, plus (ii) 7 healthy volunteers, selected to have relatively large bra cup sizes. We studied: overall body positioning, arm positioning, beam access, breast reproducibility, and comfort. Amongst the healthy volunteer cohort, the impact of specialised radiotherapy bras upon inframammary skinfolds (ISF) was also determined, for upright treatment positions. In conclusion, upright body positioning for breast radiotherapy appears to be comfortable and feasible. Of the 9 patients who received conventional, supine radiotherapy (mean age 63.5 years, maximum age 90 years), 7 reported that they preferred upright positioning. Radiotherapy bras were effective in reducing/eliminating ISF for upright body positions, including for very large breasted volunteers. For upright proton radiotherapy to the breast, beam access should be straightforward, even for arms-down treatments, as en-face field directions are typically used. For photon radiotherapy, additional research is now required to investigate beam paths and whether, for certain patients, additional immobilisation will be required to keep the contralateral breast free from exposure. Future research should also investigate arm supports custom-designed for upright radiotherapy.

Secondary Breast Angiosarcoma After a Primary Diagnosis of Breast Cancer: A Retrospective Analysis of the Surveillance, Epidemiology, and End Results (SEER) Database.

Angiosarcoma is a rare complication of breast-conserving therapy. This study evaluated the change in incidence between 1992 and 2016 of secondary breast angiosarcoma (SBA) in patients with a history of breast cancer and the impact of management strategies for the original breast carcinoma on angiosarcoma treatment. Breast cancer and angiosarcoma cases were abstracted from the Surveillance, Epidemiology, and End Result (SEER) database. SBAs were defined as angiosarcomas located in the breast occurring after a prior breast cancer diagnosis. Primary breast angiosarcomas (PBAs) were defined as an angiosarcoma diagnosis listed as "one primary only." Incidence rates were estimated using a proportion of the US total population. Survival was analyzed by the Kaplan-Meier method, and Cox proportional hazard models were used to assess the association of clinicopathologic characteristics on overall survival. Between 1992 and 2016, 193 cases of SBA were reported in the SEER dataset in patients with a prior history of breast cancer. The incidence of breast angiosarcoma in patients with a prior diagnosis of breast cancer increased 3-fold from about 10 cases per 100,000 person-years to about 30 cases per 100,000 person-years over this same period ( P =0.0037). For treatment of SBA (n=193), almost all (95%) had surgery. Nine percent received radiation (compared with 35% of patients with PBA, P <0.001) and 23% received chemotherapy (vs. 45% for PBA, P =0.11). We demonstrate an increasing incidence of SBA over the study period. These data can help inform shared decision-making for optimal management of locoregional breast cancer and raise awareness of secondary angiosarcoma.

Evaluating ChatGPT as an adjunct for the multidisciplinary tumor board decision-making in primary breast cancer cases

BackgroundAs the available information about breast cancer is growing every day, the decision-making process for the therapy is getting more complex. ChatGPT as a transformer-based language model possesses the ability to write scientific articles and pass medical exams. But is it able to support the multidisciplinary tumor board (MDT) in the planning of the therapy of patients with breast cancer?Material and MethodsWe performed a pilot study on 10 consecutive cases of breast cancer patients discussed in MDT at our department in January 2023. Included were patients with a primary diagnosis of early breast cancer. The recommendation of MDT was compared with the recommendation of the ChatGPT for particular patients and the clinical score of the agreement was calculated.ResultsResults showed that ChatGPT provided mostly general answers regarding chemotherapy, breast surgery, radiation therapy, chemotherapy, and antibody therapy. It was able to identify risk factors for hereditary breast cancer and point out the elderly patient indicated for chemotherapy to evaluate the cost/benefit effect. ChatGPT wrongly identified the patient with Her2 1 + and 2 + (FISH negative) as in need of therapy with an antibody and called endocrine therapy “hormonal treatment”.ConclusionsSupport of artificial intelligence by finding individualized and personalized therapy for our patients in the time of rapidly expanding amount of information is looking for the ways in the clinical routine. ChatGPT has the potential to find its spot in clinical medicine, but the current version is not able to provide specific recommendations for the therapy of patients with primary breast cancer.

Contralateral breast cancer risk in patients with breast cancer and a germline-BRCA1/2 pathogenic variant undergoing radiation.

Radiation-induced secondary breast cancer (BC) may be a concern after radiation therapy (RT) for primary breast cancer (PBC), especially in young patients with germline (g)BRCA-associated BC who already have high contralateral BC (CBC) risk and potentially increased genetic susceptibility to radiation. We sought to investigate whether adjuvant RT for PBC increases the risk of CBC in patients with gBRCA1/2-associated BC. The gBRCA1/2 pathogenic variant carriers diagnosed with PBC were selected from the prospective International BRCA1/2 Carrier Cohort Study. We used multivariable Cox proportional hazards models to investigate the association between RT (yes vs no) and CBC risk. We further stratified for BRCA status and age at PBC diagnosis (<40 and >40 years). Statistical significance tests were 2-sided. Of 3602 eligible patients, 2297 (64%) received adjuvant RT. Median follow-up was 9.6 years. The RT group had more patients with stage III PBC than the non-RT group (15% vs 3%, P < .001), received chemotherapy more often (81% vs 70%, P < .001), and received endocrine therapy more often (50% vs 35%, P < .001). The RT group had an increased CBC risk compared with the non-RT group (adjusted hazard ratio [HR] = 1.44; 95% confidence interval [CI] = 1.12 to 1.86). Statistical significance was observed in gBRCA2 (HR = 1.77; 95% CI = 1.13 to 2.77) but not in gBRCA1 pathogenic variant carriers (HR = 1.29; 95% CI = 0.93 to 1.77; P = .39 for interaction). In the combined gBRCA1/2 group, patients irradiated when they were younger than or older than 40 years of age at PBC diagnosis showed similar risks (HR = 1.38; 95% CI = 0.93 to 2.04 and HR = 1.56; 95% CI = 1.11 to 2.19, respectively). RT regimens minimizing contralateral breast dose should be considered in gBRCA1/2 pathogenic variant carriers.

Difficulties of Diagnosing Primary Multiple Synchronous Breast Cancer with Histological Heterogeneity of Tumors (Clinical Case)

The difficulties of timely diagnosis of primary multiple synchronous breast cancer with histological heterogeneity of tumors are demonstrated by a clinical example. Taking into account the fact that breast cancer continues to lead among all oncological pathology and accounts for 11.8% of all malignant neoplasms, diagnostic algorithms of the stage should be personalized. The presented clinical case demonstrates multidisciplinary errors committed at different stages of the patient’s examination.

Expression and Clinical Significance of TIGIT in Primary Breast Cancer.

The roles of T cell immunoreceptor with Ig and ITIM domains (TIGIT) in the diagnosis of primary breast cancer (PBC) are still unclear. This study was designed to investigate the expression of TIGIT in PBC patients, with an aim to analyze its diagnostic value in PBC. We first explore the expression of TIGIT in cancer patients based on TCGA database, and then we analyzed its correlation with clinicopathological features. Afterwards, we compared the protein and mRNA expressions of TIGIT in two BC cell lines (MCF-7 and MDA-MB-231) and normal breast epithelial cell line (MCF-10A). Subsequently, 56 PBC female patients admitted to the Taizhou People's Hospital from October 2018 to June 2021 were included in this study. Flow cytometry was used to detect TIGIT level on peripheral blood CD3+ T cells of PBC patients and healthy controls. TIGIT expression in PBC tissues was detected by immunohistochemistry (IHC) and immunofluorescence staining. TCGA database showed that compared with adjacent tissues, TIGIT was significantly upregulated in tumor tissues. High TIGIT expression was positively correlated with tumor stage and negatively correlated with recurrence free survival (RFS) and overall survival (OS). TIGIT level in BC cell lines, peripheral blood and tumor tissues of PBC patients was significantly higher than that of control (P < 0.05). TIGIT level was correlated with age (P < 0.05), rather than tumor size, pathological type, lymph node metastasis, ER, PR, HER-2, and P53. ROC curve showed that the optimal critical value of peripheral blood TIGIT for BC screening was 23.38%. Postoperative TIGIT level in peripheral blood was significantly decreased compared to the preoperative TIGIT level (P < 0.05). TIGIT was upregulated in PBC and was correlated with age. It may be a potential target for the diagnosis and immunotherapy of PBC.

Breast cancer in patients with Lynch syndrome: A single institution retrospective analysis.

e22549 Background: Lynch syndrome (LS) is associated with an increased risk of several malignancies including gastrointestinal, genitourinary, gynecologic, skin, and brain cancers. However, whether patients with LS have higher risk of developing breast cancer (BC) or not is still controversial and a relevant clinical question. Methods: From the Santa Maria alle Scotte Hospital registry, we retrospectively identified consecutive patients with LS diagnosed by detecting a germline heterozygous pathogenic or likely-pathogenic variant in MLH1, MSH2, MSH6 or PMS2 on molecular genetic testing within April 2016-January 2022. We compared our sample size to Surveillance, Epidemiology, and End Results Program (SEER) of 2017 National Cancer Institute database. Results: Overall, 43 patients with LS were identified. Of those, 11 (25.6%; 95% CI 1.58-26.72%; p &lt; 0.0001) had histologically confirmed BC, 10 (91%) of whom were hormone receptor positive tumors and BC is the only diagnosis of cancer to date. In this 11 patients median age at diagnosis was 54.5 years. 45% of 11 BC LS patients has germinal MSH2 mutation , 45% of 11% are MSH6 mutaded and has a more aggressive breast cancer. Median follow-up was 3 years and 8 months. All patients are still alive and under treatment. Conclusions: Within the limitations of a small sample size and retrospective design, our analysis suggests a significant association between patients with LS and the diagnosis of primary BC. Validation of such findings through prospective clinical studies with larger samples is warranted and would lead to fundamental modifications to LS screening and follow-up international recommendations.