A prospective cohort study to analyze the interaction of tumor-to-breast volume in breast conservation therapy versus mastectomy with reconstruction.

PURPOSE: We explored the impact of the relative volume of a tumor versus the entire breast on outcomes in patients undergoing breast conservation therapy (BCT) versus mastectomy and reconstruction (M + R). We hypothesized that there would be a threshold tumor:breast ratio (TBR) below which patient-reported outcomes (PRO) would favor BCT and above which would favor M + R. METHODS: We conducted a prospective cohort study of patients with ductal carcinoma in situ (DCIS) or invasive breast cancers undergoing BCT or M + R. A prerequisite for inclusion, analysis of tumor and breast volumes was conducted from three-dimensional magnetic resonance imaging reconstructions to calculate the TBR. Three-dimensional photography was utilized to calculate pre- and postoperative volumes and assess symmetry. Oncologic, surgical, and patient-reported outcome data were obtained from relevant BREAST-Q modules administered pre- and postoperatively. RESULTS: The BCT cohort had significantly smaller tumor volumes (p = 0.001) and lower TBRs (p = 0.001) than patients undergoing M + R overall. The M + R group, however, comprised a broader range of TBRs, characterized at lower values by patients opting for contralateral prophylactic mastectomy. Postoperative satisfaction with breasts, psychosocial, and sexual well-being scores were significantly higher in the BCT cohort, while physical well-being significantly favored the M + R cohort 480.2 ± 286.3 and 453.1 ± 392.7 days later, respectively. CONCLUSIONS: Relative to BCT, M + R was used to manage a broad range of TBRs. The relative importance of oncologic and surgical risk reduction, symmetry, and number of procedures can vary considerably and may limit the utility of TBR as a guide for deciding between BCT and M + R. Clinical Trial StatementThis study was registered with clinicaltrials.gov as "A Prospective Trial to Assess Tumor:Breast Ratio and Patient Satisfaction Following Lumpectomy Versus Mastectomy With Reconstruction", Identifier: NCT02216136.

The Future of Contrast-Enhanced Mammography.

OBJECTIVE: The purpose of this article is to discuss facilitators of and barriers to future implementation of contrast-enhanced mammography (CEM) in the United States. CONCLUSION: CEM provides low-energy 2D mammographic images analogous to digital mammography and contrast-enhanced recombined images that allow assessment of neovascularity similar to that offered by MRI. The utilization of CEM in the United States is currently low but could increase rapidly given the many potential indications for its clinical use.

Palpable breast abnormalities in women under age 40.

Although the prevalence of malignancy in average risk women under age 40 presenting with a palpable breast abnormality is low, the management of benign-appearing palpable abnormalities remains controversial. This study assesses the imaging evaluation, subsequent management, and outcomes of women under age 40 presenting with a palpable area of concern. This study also evaluates the costs, utility, and outcomes of BI-RADS 3 assessment in this patient population. A single institution retrospective case review from July 2010 through June 2013 identified women under age 40 presenting with a new palpable breast abnormality. Diagnostic imaging evaluation was performed. BI-RADS assessments and recommendations were recorded prospectively. Outcome was determined by tissue diagnosis, 2 years of surveillance, or search of the hospital tumor registry. Performance measures were calculated. Among 1440 cases, 1052 were initially assessed as BI-RADS 1 or 2 (73.1%), 184 as BI-RADS 3 (12.8%), 182 as BI-RADS 4 (12.6%), and 22 as BI-RADS 5 (1.5%). In all, 30 breast malignancies were diagnosed (cancer yield 2.1%). All 30 cancers were initially categorized as BI-RADS 4 or 5. No BI-RADS 1, 2, or 3 findings proved malignant. The imaging evaluation sensitivity was 100%, specificity was 87.7%, and accuracy was 87.9%. The negative predictive value was 100% and the positive predictive value was 14.7%. Average risk women under age 40 presenting with a palpable abnormality have a low prevalence of breast cancer. Imaging evaluation has a high sensitivity and negative predictive value, thereby allowing for confident characterization and appropriate management recommendations. For palpable solid masses with benign imaging features in women under age 40, short-term interval follow-up with subsequent periodic imaging or clinical examination for a total of 2 years is a cost-effective and safe alternative to biopsy.

Plasma carotenoids and the risk of premalignant breast disease in women aged 50 and younger: a nested case-control study.

PURPOSE: To examine the association of plasma carotenoids, micronutrients in fruits, and vegetables, with risk of premalignant breast disease (PBD) in younger women. METHODS: Blood samples were collected at the Siteman Cancer Center between 2008 and 2012 from 3537 women aged 50 or younger with no history of cancer or PBD. The analysis included 147 participants diagnosed with benign breast disease or breast carcinoma in situ during a 27-month follow-up and 293 controls. Cases and controls were matched on age, race/ethnicity, and date of and fasting status at blood draw. Plasma carotenoids were quantified. We used logistic regression to calculate odds ratios (ORs) and 95% confidence intervals (CIs) and linear regression to assess racial differences in plasma carotenoids. RESULTS: The risk reduction between the highest and lowest tertiles varied by carotenoid, with ß-cryptoxanthin having the greatest reduction (OR 0.62; 95% CI, 0.62-1.09; P trend = 0.056) and total carotenoids the least (OR 0.83; 95% CI, 0.48-1.44; P trend = 0.12). We observed an inverse association between plasma carotenoids and risk of PBD in obese women (BMI ≥ 30 kg/m2; 61 cases and 115 controls) but not lean women (BMI < 25 kg/m2; 54 cases and 79 controls), although the interaction was not statistically significant. Compared to white women, black women had lower levels of α and ß-carotene and higher levels of ß-cryptoxanthin and lutein/zeaxanthin. CONCLUSIONS: We observed suggestive inverse associations between plasma carotenoids and risk of PBD in younger women, consistent with inverse associations reported for invasive breast cancer. Carotenoids may play a role early in breast cancer development.

Predictors of false negative axillary ultrasound in breast cancer.

BACKGROUND: We sought to identify clinicopathologic factors related to false negative axillary ultrasound (AUS) results. METHODS: Patients with a clinically node-negative stage I-II breast cancer who also had a normal AUS were identified from our prospectively maintained database. All AUS studies were interpreted by dedicated breast radiologists as "normal" according to the absence of specific characteristics shown to be commonly associated with metastatic involvement. True- and false-negative AUS studies were compared statistically based on clinical, radiographic, and histologic parameters. RESULTS: Of the 118 patients with a normal AUS, 25 (21%) were ultimately found to be node-positive on pathologic assessment after axillary surgery. On bivariate analysis, primary tumor size and lymphovascular invasion (LVI) were found to be significantly different between true- and false-negative AUS. The average tumor size was smaller in the true-negative group compared with that in the false-negative group (16 versus 21 mm [P < 0.01]). The presence of LVI was more likely in the false-negative group (44%) compared with that in the true-negative group (8%, P < 0.0001). No significant difference was noted between groups with regard to patient age, race, body mass index, tumor grade, histologic type, hormone receptor status, and time between AUS and axillary surgery. On multivariate analysis, only the presence of LVI achieved statistical significance (P = 0.0007). CONCLUSIONS: AUS is a valuable tool that accurately predicted absence of axillary disease in 79% of patients with clinically node-negative breast cancer. AUS findings may be less accurate in the setting of LVI, and a negative AUS in patients with LVI should be interpreted cautiously.

Recent trends in adherence to continuous screening for breast cancer among Medicare beneficiaries.

OBJECTIVE: The aim of this study is to examine recent trends in adherence to continuous screening, especially the rate of subsequent screening mammography following an initial screening before and after the U.S. Preventive Services Task Force (USPSTF) revised its guidelines on breast cancer in November 2009. METHODS: We retrospectively analyzed Medicare fee-for-service claims data to: 1) compare rate of subsequent screening mammography over 27 month periods for 317,150 women screened in either 2004 or 2009; and 2) examine patterns of subsequent screening by age and race. RESULTS: When adjusted for age, race, state of residence, county-level covariates, and clustered on ordering provider, the rate of subsequent screening decreased in 2009 relative to 2004 (OR=0.75; 95% CI: 0.74-0.76). Adjusted odds ratios are similar for alternative follow-up windows (15 months, 0.71; 24 months, 0.70; 30 months 0.75). The decline was mostly attributable to women 75 and older who are now less likely to return for a subsequent screening. Although USPSTF guidelines call for 24 months, approximately half of women continue screening at 12-month intervals in both cohorts. CONCLUSIONS: The rate of subsequent screening mammography has declined after 2009. Older women seem to follow the revised USPSTF guideline, but confusion by physicians and patients about competing guidelines may be contributing to these findings.

A Semiautonomous Deep Learning System to Reduce False Positives in Screening Mammography.

Purpose To evaluate the ability of a semiautonomous artificial intelligence (AI) model to identify screening mammograms not suspicious for breast cancer and reduce the number of false-positive examinations. Materials and Methods The deep learning algorithm was trained using 123 248 two-dimensional digital mammograms (6161 cancers) and a retrospective study was performed on three nonoverlapping datasets of 14 831 screening mammography examinations (1026 cancers) from two U.S. institutions and one U.K. institution (2008-2017). The stand-alone performance of humans and AI was compared. Human plus AI performance was simulated to examine reductions in the cancer detection rate, number of examinations, false-positive callbacks, and benign biopsies. Metrics were adjusted to mimic the natural distribution of a screening population, and bootstrapped CIs and P values were calculated. Results Retrospective evaluation on all datasets showed minimal changes to the cancer detection rate with use of the AI device (noninferiority margin of 0.25 cancers per 1000 examinations: U.S. dataset 1, P = .02; U.S. dataset 2, P < .001; U.K. dataset, P < .001). On U.S. dataset 1 (11 592 mammograms; 101 cancers; 3810 female patients; mean age, 57.3 years ± 10.0 [SD]), the device reduced screening examinations requiring radiologist interpretation by 41.6% (95% CI: 40.6%, 42.4%; P < .001), diagnostic examinations callbacks by 31.1% (95% CI: 28.7%, 33.4%; P < .001), and benign needle biopsies by 7.4% (95% CI: 4.1%, 12.4%; P < .001). U.S. dataset 2 (1362 mammograms; 330 cancers; 1293 female patients; mean age, 55.4 years ± 10.5) was reduced by 19.5% (95% CI: 16.9%, 22.1%; P < .001), 11.9% (95% CI: 8.6%, 15.7%; P < .001), and 6.5% (95% CI: 0.0%, 19.0%; P = .08), respectively. The U.K. dataset (1877 mammograms; 595 cancers; 1491 female patients; mean age, 63.5 years ± 7.1) was reduced by 36.8% (95% CI: 34.4%, 39.7%; P < .001), 17.1% (95% CI: 5.9%, 30.1%: P < .001), and 5.9% (95% CI: 2.9%, 11.5%; P < .001), respectively. Conclusion This work demonstrates the potential of a semiautonomous breast cancer screening system to reduce false positives, unnecessary procedures, patient anxiety, and medical expenses. Keywords: Artificial Intelligence, Semiautonomous Deep Learning, Breast Cancer, Screening Mammography Supplemental material is available for this article. Published under a CC BY 4.0 license.

Axillary ultrasound in patients with clinically node-negative breast cancer: which features are predictive of disease?

BACKGROUND: Axillary ultrasound is used in the evaluation of breast cancer patients to identify subclinical node-positive disease. The study aim was to identify whether certain radiologic characteristics correlate with cytology and final pathology. METHODS: We retrospectively reviewed ultrasound images of 110 women with clinically node-negative breast cancer and suspicious axillary ultrasound to identify specific anatomic characteristics previously shown to be more commonly associated with metastatic involvement. Results were compared with cytology and final pathology. We used descriptive statistics for data summary. RESULTS: Of the 110 patients, cytology was positive in 71 (68%) and final pathology was positive in 80 (73%). The most common indication for biopsy was lymph node cortex characterized by thickening or eccentric contour (N = 40). Loss of the fatty hilum was described in 17 patients, and 9 patients had lymph nodes with both abnormal cortical and hilar features. Of 43 patients with "suspicious" disease without specific criteria, the most common indication for biopsy was disparity in size of one or more lymph nodes compared with others. Maximum cortical thickness was greater in patients with positive cytology compared with those with negative cytology (7.6 versus 6.2 mm; P = 0.047). Ultrasound characteristics such as lymph node size, cortical morphology, contour, and hilar fat were not individually predictive of final cytology and pathology. CONCLUSIONS: Axillary ultrasound is a valuable tool that accurately predicted malignant axillary disease in 73% of patients with clinically node-negative breast cancer. Elaboration of standard criteria for nodal evaluation will improve usefulness of this imaging modality in preoperative staging of the axilla.

Pathologic outcomes of nonmalignant papillary breast lesions diagnosed at imaging-guided core needle biopsy.

PURPOSE: To determine the upstage rate from nonmalignant papillary breast lesions obtained at imaging-guided core needle biopsy (CNB) and if there are any clinical, imaging, or pathologic features that can be used to predict eventual upstaging to malignancy. MATERIALS AND METHODS: This retrospective case review was institutional review board approved and HIPAA compliant, with a waiver of informed consent. A database search (from January 2001 to March 2010) was performed to find patients with a nonmalignant papillary breast lesion diagnosed at CNB. Of the resulting 128 patients, 86 (67%) underwent surgical excision; 42 (33%) patients were observed with imaging, for a median observation time of 4.1 years (range, 1.0-8.6 years). Chart review was performed to determine pertinent features of each case. RESULTS: Fourteen of 128 patients were subsequently found to have malignancy at excision, for an upstage rate of 11%. Nine (7%) of the 128 patients were subsequently found to have atypia at excision. Comparisons between patients with upstaged lesions and patients whose lesions were not upstaged demonstrated patients with upstaged lesions to be slightly older (65 vs 56 years, P=.01), more likely to have a mass than calcifications at imaging (P=.03), and to have had less tissue obtained at biopsy (three vs five cores obtained, P=.02; 14- vs 9-gauge needle used, P<.01; no vacuum assistance used, P<.01). Most strongly predictive of eventual malignancy, however, was whether the interpreting pathologist qualified the benign diagnosis at CNB with additional commentary (P<.01). CONCLUSION: Given the substantial upstage rate (11%) of papillary lesions diagnosed at imaging-guided CNB, surgical excision is an appropriate management decision; however, careful evaluation in concert with an expert breast pathologist may allow for observation in appropriately selected patients.

Positive margin rates following breast-conserving surgery for stage I-III breast cancer: palpable versus nonpalpable tumors.

BACKGROUND: Margin status is a significant risk factor for local recurrence. We sought to examine whether the method of tumor localization predicted the margin status and the need for re-excision for both nonpalpable and palpable breast cancer. METHODS: We identified 358 consecutive breast cancer patients who were treated with breast-conserving therapy (BCT) from 1999 to 2006. Data included patient and tumor characteristics, method of localization (needle versus palpation), and pathologic outcomes. Descriptive statistics were used for data summary and data were compared using χ(2). RESULTS: Of 358 patients undergoing BCT, 234 (65%) underwent needle localization for a nonpalpable tumor and 124 (35%) underwent a palpation-guided procedure. Patients undergoing palpation-guided procedures were younger and had larger tumors at a more advanced pathologic stage of disease than those undergoing needle localization procedures (P < 0.05 for each). Patient race, tumor grade, presence of lymphovascular invasion, biomarker profile, and nodal status were not significantly different between the two groups (P > 0.05). Overall, 137 patients (38%) had one or more positive margins: 90 of 234 (38%) who had a needle localization procedure and 47 of 124 (38%) who had a palpation-guided procedure (P > 0.05). The number of margins affected did not differ significantly between the two groups. CONCLUSION: Although patients with palpable breast cancer had larger tumors than those with nonpalpable breast cancer, the incidence and number of positive margins was similar to those who had needle localization for nonpalpable tumors. Improved methods of localization are needed to reduce the rate of positive margins and the need for re-excision.

Recent Trends in Screening Breast MRI.

OBJECTIVE: The objective of this study was to assess trends in screening breast MRI utilization among privately insured women in the U.S. from 2007 to 2017. METHODS: The utilization of screening breast MRI among women aged 25-64 years from January 1, 2007, to December 31, 2017, was obtained using the MarketScan Commercial Database. We used Current Procedural Terminology codes to exclude breast MRI exams performed in women with a new breast cancer diagnosis and in women imaged to assess response to neoadjuvant therapy in the preceding 90 days. During the 11-year study, 351 763 study-eligible women underwent 488 852 MRI scans. RESULTS: An overall 55.0% increase in screening breast MRI utilization was observed over the study period, with a steadily increasing trend. The greatest annual increase in percent utilization was from 2007 to 2008 at 16.6%. The highest utilization rate was in 2017, in which 0.4% of women aged 25-64 years underwent screening breast MRI. Of the women who underwent screening MRI with sufficient follow-up, 76.5% underwent only one examination during the study period. CONCLUSION: Utilization of screening breast MRI has increased steadily in the past decade to a peak of 0.4% of adult women. However, an estimated 9% of U.S. women are eligible for high-risk breast MRI screening; thus, utilization falls short of optimal compliance. Further studies to evaluate the barriers to screening compliance may help optimize utilization.

Utility of breast MRI for evaluation of residual disease following excisional biopsy.

BACKGROUND: Because benign postoperative changes may overlap those of malignancy, the utility of breast MRI following an excisional biopsy is unclear. We sought to investigate the ability of MRI to predict residual disease following an excisional biopsy for breast cancer. MATERIALS AND METHODS: We reviewed 93 patients who underwent surgical treatment for stage 0-III breast cancer at our institution from January 2005 to May 2008. All patients had previously undergone excisional biopsy with subsequent MRI. Patient, tumor, and treatment characteristics were collected. Descriptive statistics were utilized for data summary and data were compared using Fisher's exact or χ(2) tests. RESULTS: The mean age of the 84 patients who had additional surgery following MRI was 51 ± 7 y. Thirteen (15%) patients had only postoperative changes on MRI; six had residual disease on final pathology. Of 71 patients with MRI findings suspicious for residual disease, 54 (76%) had pathologic confirmation, while 17 (24%) had only benign pathology. The sensitivity and specificity of MRI following excisional biopsy were 90% and 29%, respectively. Overall, 49 (58%) of the 84 patients underwent mastectomy, including 11 of 24 (46%) with negative final pathology. Patient age, tumor size, tumor grade, biomarker profile, nodal status, and MRI findings were not predictive of surgical treatment type (P > 0.05). CONCLUSION: Although excisional biopsy decreases the specificity of breast MRI, its sensitivity remains high. Nearly 50% of patients with a suspicious MRI and negative final pathology underwent mastectomy, suggesting that additional biopsy of all suspicious MRI findings is necessary to avoid surgical overtreatment.

Adiposity Change Over the Life Course and Mammographic Breast Density in Postmenopausal Women.

Mammographic breast density is a strong risk factor for breast cancer. We comprehensively investigated the associations of body mass index (BMI) change from ages 10, 18, and 30 to age at mammogram with mammographic breast density in postmenopausal women. We used multivariable linear regression models, adjusted for confounders, to investigate the associations of BMI change with volumetric percent density, dense volume, and nondense volume, assessed using Volpara in 367 women. At the time of mammogram, the mean age was 57.9 years. Compared with women who had a BMI gain of 0.1-5 kg/m2 from age 10, women who had a BMI gain of 5.1-10 kg/m2 had a 24.4% decrease [95% confidence interval (CI), 6.0%-39.2%] in volumetric percent density; women who had a BMI gain of 10.1-15 kg/m2 had a 46.1% decrease (95% CI, 33.0%-56.7%) in volumetric percent density; and women who had a BMI gain of >15 kg/m2 had a 56.5% decrease (95% CI, 46.0%-65.0%) in volumetric percent density. Similar, but slightly attenuated associations were observed for BMI gain from ages 18 and 30 to age at mammogram and volumetric percent density. BMI gain over the life course was positively associated with nondense volume, but not dense volume. We observed strong associations between BMI change over the life course and mammographic breast density. The inverse associations between early-life adiposity change and volumetric percent density suggest that childhood adiposity may confer long-term protection against postmenopausal breast cancer via its effect of mammographic breast density.

Focal breast pain: imaging evaluation and outcomes.

OBJECTIVES: To determine the number and characteristics of cancers detected and the optimal imaging evaluation in women presenting with focal breast pain (FBP). MATERIALS AND METHODS: We performed a retrospective review of 4720 women who underwent imaging for FBP from 2001 to 2013. Women 18 and over with one or two foci of breast pain and no concurrent breast symptoms were included. 944 patients met criteria. We recorded the imaging work-up, presence and type of finding at the site of pain, BI-RADS® assessment, and pathological outcomes. Subsequent imaging and clinical follow up was recorded. RESULTS: Imaging evaluation consisted of sonogram alone in 286 women, mammogram alone in 231 women, and both in 427 women. 113 women had an imaging finding at the site of pain; 103 were designated benign or probably benign. 12 biopsies of corresponding findings were performed: 9 benign, 1 invasive lobular carcinoma, 1 invasive ductal carcinoma, 1 ductal carcinoma in situ. All three malignancies were seen mammographically; 2 had an ultrasound correlate. At initial evaluation, 4 incidental breast cancers were diagnosed remote from the site of FBP. All were seen on mammogram and 2 of 4 had an ultrasound correlate. On follow up evaluation, 9 cancers were diagnosed at the site of pain and 13 incidental cancers were diagnosed. CONCLUSION: FBP is rarely associated with malignancy. Targeted ultrasound may be deferred in women 40 and older with FBP, no other clinical findings, and a negative mammogram.

American College of Radiology Accreditation, Performance Metrics, Reimbursement, and Economic Considerations in Breast MR Imaging.

Accreditation through the American College of Radiology (ACR) Breast Magnetic Resonance Imaging Accreditation Program is necessary to qualify for reimbursement from Medicare and many private insurers and provides facilities with peer review on image acquisition and clinical quality. Adherence to ACR quality control and technical practice parameter guidelines for breast MR imaging and performance of a medical outcomes audit program will maintain high-quality imaging and facilitate accreditation. Economic factors likely to influence the practice of breast MR imaging include cost-effectiveness, competition with lower-cost breast-imaging modalities, and price transparency, all of which may lower the cost of MR imaging and allow for greater utilization.

Circulating Receptor Activator of Nuclear Factor-κB (RANK), RANK ligand (RANKL), and Mammographic Density in Premenopausal Women.

The receptor activator of nuclear factor-κB (RANK) pathway plays essential roles in breast development. Mammographic density is a strong risk factor for breast cancer, especially in premenopausal women. We, therefore, investigated the associations of circulating RANK and soluble RANK ligand (sRANKL) with mammographic density in premenopausal women. Mammographic density was measured as volumetric percent density in 365 cancer-free premenopausal women (mean age, 47.5 years) attending screening mammogram at the Washington University School of Medicine (St. Louis, MO). We used linear regression models adjusted for confounders, to compare the least-square means of volumetric percent density across tertiles of circulating RANK and sRANKL. Furthermore, because RANKL levels in mammary tissue are modulated by progesterone, we stratified analyses by progesterone levels. The mean volumetric percent density increased across tertiles of circulating RANK from 8.6% in tertile 1, to 8.8% in tertile 2, and 9.5% in tertile 3 (P trend = 0.02). For sRANKL, the mean volumetric percent density was 8.5% in tertile 1, 9.4% in tertile 2, and 9.0% in tertile 3 (P trend = 0.30). However, when restricted to women with higher progesterone levels, the mean volumetric percent density increased from 9.1% in sRANKL tertile 1 to 9.5% in tertile 2, and 10.1% in tertile 3 (P trend = 0.01). Circulating RANK was positively associated with volumetric percent density, while circulating sRANKL was positively associated with volumetric percent density among women with higher progesterone levels. These findings support the inhibition of RANKL signaling as a pathway to reduce mammographic density and possibly breast cancer incidence in high-risk women with dense breasts.

Adiposity at Age 10 and Mammographic Density among Premenopausal Women.

Although childhood adiposity is inversely associated with breast cancer risk, the association of childhood adiposity with mammographic density in premenopausal women has not been adequately studied. We analyzed data from 365 premenopausal women who came in for screening mammography at Washington University (St. Louis, MO) from 2015 to 2016. Body size at age 10 was self-reported using somatotype pictogram. Body mass index (BMI) at age 10 was imputed using data from Growing Up Today Study. Volpara software was used to evaluate volumetric percent density (VPD), dense volume (DV), and nondense volume (NDV). Adjusted multivariable linear regression models were used to evaluate the associations between adiposity at age 10 and mammographic density measures. Adiposity at age 10 was inversely associated with VPD and positively associated with NDV. A 1 kg/m2 increase in BMI at age 10 was associated with a 6.4% decrease in VPD, and a 6.9% increase in NDV (P < 0.001). Compared with women whose age 10 body size was 1 or 2, women with body size 3 or 4 had a 16.8% decrease in VPD and a 26.6% increase in NDV, women with body size 5 had a 32.2% decrease in VPD and a 58.5% increase in NDV, and women with body sizes ≥6 had a 47.8% decrease in VPD and a 80.9% increase in NDV (P < 0.05). The associations were attenuated, but still significant after adjusting for current BMI. Mechanistic studies to understand how childhood adiposity influences breast development, mammographic density, and breast cancer in premenopausal women are needed. Cancer Prev Res; 11(5); 287-94. ©2018 AACR.