Aug 2026· Cancer Epidemiology, Biomarkers and Prevention· 0 citations
Medicine
TL;DR
Advancing knowledge of specific BBD diagnoses may improve breast cancer risk prediction and support targeted screening and prevention strategies.
Abstract
Background
Benign breast disease (BBD) increases breast cancer risk; however, associations between specific BBD diagnoses and breast cancer risk are insufficiently studied.
Methods
We analyzed 131,075 benign breast biopsy episodes from 1994-2022 identified from eight Breast Cancer Surveillance Consortium registries. Pathological diagnoses were classified into 38 BBDs within 4 categories. For comparison, women with no prior breast biopsy and a negative screening mammogram (N=1,599,694) were identified. Associations of BBDs with invasive breast carcinoma and ductal carcinoma in situ (DCIS) were estimated using Fine-Gray competing risk models.
Results
Over a median follow-up of 7.5 years, 35,251 invasive breast cancers and 9,743 DCIS cases occurred. Lobular carcinoma in situ was associated with a 5.61-fold (95% confidence interval [CI]: 4.10-7.68) increased risk of invasive carcinoma and an 8.82-fold (95% CI: 5.39-14.4) increased risk of DCIS. Among proliferative changes with atypia BBDs, invasive cancer hazard ratios (HRs) ranged from 2.76-4.85; DCIS HRs, 5.07-8.51. Among proliferative changes without atypia BBDs, invasive HRs ranged from near-null (papillomatosis) to moderate and strong associations (e.g., HR=1.55 for usual ductal hyperplasia and 2.84 for multiple papillomas); DCIS HRs=1.37-5.04. Nonproliferative BBDs were associated with low-to-moderate risk (invasive HRs=0.63 for atrophy to 2.16 for benign breast parenchyma; DCIS HRs=0.66-4.29). Most associations declined with increasing time since biopsy.
Conclusions
Associations between BBDs and breast cancer varied widely within commonly used histologic categories.
IMPACT
Advancing knowledge of specific BBD diagnoses may improve breast cancer risk prediction and support targeted screening and prevention strategies.
A meta-analysis of the existing literature was conducted to quantify breast cancer risk according to histologic subtype of benign breast disease (BBD) among women of diverse racial and ethnic backgrounds worldwide. PubMed (Medline), EMBASE (Emtree), and other relevant biomedical databases were searched through February 2026 to identify studies reporting the development of subsequent breast cancer in women diagnosed with either nonproliferative disease (NP), proliferative disease without atypia (PDWA), or atypical hyperplasia (AH). Seven studies met the eligibility criteria. Women of Asian ancestry with PDWA or AH had a substantially higher risk of breast cancer than those with NP. Among Black women, breast cancer risk associated with BBD subtypes was comparable to historically reported risks among White women, whereas associations among Hispanic women were less clear due to greater data limitations. The variable BBD-associated breast cancer risk across racial groups warrants confirmation and underscores the need for further investigation of the mechanisms underlying these differences.
A. Koric, Nusrat Preema, A. Anandarajah et al.· Research Square· 0 citations
Breast cancer risk after ovarian cancer in germline BRCA1/2 heterozygotes remains uncertain, with a recent large multicentre international study reporting lower-than-expected incidence in the first decade after ovarian cancer diagnosis (Apostol et al. 2026). We re‑evaluated our previously published regional cohort of 701 women with ovarian cancer and a germline BRCA1/2 pathogenic or likely pathogenic variant, restricting the analysis to those tested after ovarian cancer diagnosis and without prior breast cancer, to minimise ascertainment and survivor bias. In our refined cohort of 406 women, 19 breast cancers occurred over 1340.97 person‑years, giving an annual incidence of 1.42% (1.60% for BRCA1 and 1.14% for BRCA2). Incidence was lowest within the first 5 years (0.88%/year) and increased beyond 10 years (1.89%/year). These estimates align closely with those reported recently by Apostol et al. Breast cancer incidence after ovarian cancer is low in the first decade but may rise thereafter. These findings support reassurance during early survivorship while recognising that long‑term survivors may still consider risk‑reducing mastectomy.
Robert D. Morgan, E. Woodward, D. G. Evans· Journal of Medical Genetics· 0 citations
Higher breast density was associated with later age at menarche, nulliparity, breastfeeding, history of benign breast disease, alcohol consumption, lower body mass index (BMI) at recruitment and at age 20, and current use of menopausal hormone therapy (MHT).
L. Johns, Martina Brayley, R. Frost et al.· Breast Cancer Research· 0 citations
BACKGROUND
Breast cancer is the most common malignancy among U.S. women, and survivors face increased risk for subsequent malignancies, including lung cancer. Prior studies have reported associations between breast cancer treatments and lung cancer, but contemporary data remain limited. This study evaluates lung cancer risk following breast cancer, stratified by treatment modality, within an integrated health system.
METHODS
A retrospective cohort study of women diagnosed with breast cancer from 2010-2021 was conducted within Kaiser Permanente Northern California. Exclusion criteria included prior or early post-diagnosis lung cancer, early death, or lack of health plan membership. The primary outcome was subsequent primary lung cancer. Cumulative incidence was estimated using competing-risk methods, with death as a competing event. Associations with breast cancer treatments were evaluated using Fine-Gray regression.
RESULTS
Among 42,290 women followed for a median of 4.6 years, 324 (0.8%) developed lung cancer. The five-year cumulative incidence was 0.66%, with the highest incidence among current smokers (2.9%) and women aged 65-74 years and ≥75 years (1.1% and 1.2%, respectively). After adjusting for demographic, clinical, and tumor-related factors, breast cancer treatment exposures were not associated with lung cancer. Hispanic women demonstrated a significantly lower hazard of lung cancer compared with White women (HR 0.54, 95% CI 0.33-0.88).
CONCLUSIONS
Lung cancer risk among breast cancer survivors has increased over time, however risk was driven by patient-level factors, rather than breast cancer treatment exposures.
Andrea M. Gochi, Tanran Wang, Hyunjee V. Kwak et al.· Annals of Thoracic Surgery· 0 citations
OBJECTIVE
Breast cancer method of detection (MOD) describes how a cancer is first identified: through screening or non-screening (symptomatic/incidental) presentation. We examined associations between MOD and patient demographics, tumor characteristics, treatment patterns, and survival.
METHODS
This retrospective cohort study included women ≥40 years diagnosed with breast cancer between 1/2019 and 12/2021, follow-up through 7/2026. MOD was classified as screen-detected or non-screen-detected. Logistic regression and chi-square tests evaluated associations with patient, tumor, and treatment variables. Kaplan-Meier and multivariable Cox regression assessed all-cause survival.
RESULTS
Among 1,023 women (mean age 63.5 ± 12.1 years), screen-detected cancers (n=710, 69.4%) had more favorable characteristics: earlier T stage (T0: 26.3% vs. 5.4%, p<0.001), negative lymph nodes (N0: 85.5% vs. 59.1%, p<0.001), fewer metastases (M0: 98.6% vs. 82.4%, p<0.001), and lower grade (grade 1: 18.6% vs. 7.4%, p<0.001). More received lumpectomy (72.1% vs. 50.2%, p<0.001) and fewer received neoadjuvant chemotherapy (5.2% vs. 22.5%, p<0.001). Non-screen-detected cancers were more common among the unemployed (21.0% vs. 14.0%, p=0.001), uninsured (3.8% vs. 1.7%, p=0.026), and women ≥75 years (23.3% vs. 16.1%, p=0.019). Within non-screen-detected cancers, tumor stage worsened with time since last negative screen (p<0.001). Screen-detected cancers showed superior all-cause survival (5-year: 92.9% vs. 73.6%, p<0.001). After adjustment, screen-detection was independently associated with 43% lower mortality (HR=0.57, p=0.003). Significant survival benefit persisted in women ≥75 years (HR=0.44, p=0.014).
DISCUSSION
Screen-detected breast cancers were associated with favorable biology, less aggressive treatment, and improved survival. These findings can inform screening guidelines and underscore the importance of incorporating MOD into cancer registries.
Babita Panigrahi, Alexandra DiTommaso, N. Ghuman et al.· Journal of the American Coll...· 0 citations
Objectives: Women with a history of breast cancer are at increased risk of developing subsequent breast cancer, including ipsilateral recurrence and contralateral new primary breast cancer. This study evaluated the discriminatory performance of a mammogram-based artificial intelligence (AI) risk model for predicting subsequent breast cancer within one year after a negative screening mammogram. Methods: This enriched retrospective case–control study included women with a prior history of breast cancer who underwent screening digital breast tomosynthesis between January 2018 and December 2023 at three affiliated academic breast imaging centers. Digital breast tomosynthesis examinations classified as BI-RADS 1 or 2 were retrospectively analyzed using the ProFound AI® Risk model version 1.0 to estimate 1-year breast cancer risk. Patients were classified according to whether they developed subsequent breast cancer within one year of the index screening examination. Model discrimination was evaluated using receiver operating characteristic analysis. Sensitivity, specificity, positive predictive value, and negative predictive value were calculated at an exploratory cutoff selected by maximizing the Youden index. Results: The study included 96 women (mean age, 65.3 ± 8.7 years), of whom 32 developed subsequent breast cancer within one year, and 64 did not. The mean AI risk score was significantly higher in the subsequent breast cancer group than in the control group (1.18 ± 0.59 vs. 0.49 ± 0.41; p < 0.001). The AI model demonstrated an AUC of 0.824 (95% CI: 0.728–0.921). At an exploratory cutoff of 0.39, sensitivity was 81.3%, specificity was 76.6%, PPV was 63.4%, and NPV was 89.1%. In separate exploratory analyses, the AUC was 0.790 (95% CI: 0.641–0.939) for ipsilateral recurrence and 0.860 (95% CI: 0.752–0.974) for contralateral new primary breast cancer. AI risk scores were not significantly correlated with tumor size or age at subsequent breast cancer diagnosis. Conclusions: In this enriched retrospective case–control study, higher mammogram-based AI risk scores were associated with subsequent breast cancer within one year after a negative screening examination. The model demonstrated discriminatory performance for both ipsilateral recurrence and contralateral new primary breast cancer; however, these analyses were exploratory. Because the cohort was enriched for subsequent breast cancer events, the reported predictive values are specific to the study sample and should not be extrapolated to routine surveillance populations. Larger prospective cohorts are needed to validate discrimination, calibration, and clinical utility.
S. Ogunlade, A. Dakkak, Amie Leon et al.· Journal of Clinical Medicine· 0 citations
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