Abstract 4176: Timing of pregnancy-related factors and breast cancer risk for women across a range of absolute risk
Bibliographic record
Abstract
Abstract Background: Studies in women with pathogenic variants in BRCA1 or BRCA2 suggest that underlying breast cancer (BC) risk modifies the associations between pregnancy-related factors and BC risk. Less is known about whether the associations are modified across a range of predicted absolute BC risk based on age and the extent of BC family history. Objective: Examine the association between pregnancy-related factors and BC risk and modification by predicted absolute BC risk in the Prospective Family Study Cohort (ProF-SC) with women enrolled between 1992-2011 and a median 10.0 years of follow-up time. Methods: ProF-SC includes the six international sites of the Breast Cancer Family Registry [USA, Canada, and Australia] and the Kathleen Cuningham Foundation Consortium for Research into Familial Breast Cancer (kConFab). 17,274 women with 943 prospectively ascertained BC cases were eligible for the prospective analysis with 87% of cases self-identifying as non-Hispanic White. Questionnaires at study entry assessed self-reported pregnancy-related factors (parity, number of full-term pregnancies (FTP), age at first FTP, years since last FTP, breastfeeding, and age at menarche). We used Cox proportional hazards regression models with age as a time scale to estimate Hazard Ratios (HR) and the 95% Confidence Intervals (CI) for each reproductive variable (main effect) and examined modification by predicted absolute risk of BC, measured by a 1-year absolute risk score (continuous) estimated by the BOADICEA (interaction effect). We also examined associations stratified by estrogen receptor (ER) subtype. Results: Women with a first FTP at age ≥30 vs. <20 years had an increased risk of BC (HR=1.49, 95% CI 1.10, 2.02); no other pregnancy-related factors were associated with BC risk. Compared to nulliparous women, the main effect for higher parity was associated with increased ER-negative BC (PARS*≥4 FTP HR 2.34, 95% CI 1.09, 5.01). In contrast, increasing absolute BC risk for women with higher parity was associated with reduced risk of ER-negative BC (PARS*≥4 FTP HRinteraction 0.66, 95% CI 0.48, 0.90; pinteraction=0.01). Increasing absolute BC risk for nulliparous or first FTP at age ≥25 years had a >20% increased risk of ER-negative BC compared to first FTP at age <20 years (pinteraction=0.002); the main effects for nulliparity and first FTP at age ≥25 years and ER-negative BC were null (p-values=0.2-1.0). Compared to nulliparous women, increasing absolute risk for women who were within 5 years of their last FTP was positively associated with ER-negative BC (HRinteraction=1.54, 95% CI 1.03, 2.31); main effects were null (HR=1.00, 95% CI 0.39, 2.54). Conclusion: The association between pregnancy-related factors and BC risk are modified by predicted absolute BC risk, with stronger associations observed for ER-negative BC. Women at higher absolute BC risk may benefit from more frequent BC monitoring following childbirth. Citation Format: Jasmine A. McDonald, Yuyan Liao, Esther M. John, Allison W. Kurian, Jeanine M. Genkinger, Saundra S. Buys, John L. Hopper, kConFab Investigators, Mary Beth Terry. Timing of pregnancy-related factors and breast cancer risk for women across a range of absolute risk. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 4176.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.005 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.002 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".