Development and evaluation of a method to assess breast cancer risk using a longitudinal history of mammographic density: a cohort study.

BACKGROUND: Women with dense breasts have an increased risk of breast cancer. However, breast density is measured with variability, which may reduce the reliability and accuracy of its association with breast cancer risk. This is particularly relevant when visually assessing breast density due to variation in inter- and intra-reader assessments. To address this issue, we developed a longitudinal breast density measure which uses an individual woman's entire history of mammographic density, and we evaluated its association with breast cancer risk as well as its predictive ability. METHODS: In total, 132,439 women, aged 40-73 yr, who were enrolled in Kaiser Permanente Washington and had multiple screening mammograms taken between 1996 and 2013 were followed up for invasive breast cancer through 2014. Breast Imaging Reporting and Data System (BI-RADS) density was assessed at each screen. Continuous and derived categorical longitudinal density measures were developed using a linear mixed model that allowed for longitudinal density to be updated at each screen. Predictive ability was assessed using (1) age and body mass index-adjusted hazard ratios (HR) for breast density (time-varying covariate), (2) likelihood-ratio statistics (ΔLR-χ2) and (3) concordance indices. RESULTS: In total, 2704 invasive breast cancers were diagnosed during follow-up (median = 5.2 yr; median mammograms per woman = 3). When compared with an age- and body mass index-only model, the gain in statistical information provided by the continuous longitudinal density measure was 23% greater than that provided by BI-RADS density (follow-up after baseline mammogram: ΔLR-χ2 = 379.6 (degrees of freedom (df) = 2) vs. 307.7 (df = 3)), which increased to 35% (ΔLR-χ2 = 251.2 vs. 186.7) for follow-up after three mammograms (n = 76,313, 2169 cancers). There was a sixfold difference in observed risk between densest and fattiest eight-category longitudinal density (HR = 6.3, 95% CI 4.7-8.7), versus a fourfold difference with BI-RADS density (HR = 4.3, 95% CI 3.4-5.5). Discriminatory accuracy was marginally greater for longitudinal versus BI-RADS density (c-index = 0.64 vs. 0.63, mean difference = 0.008, 95% CI 0.003-0.012). CONCLUSIONS: Estimating mammographic density using a woman's history of breast density is likely to be more reliable than using the most recent observation only, which may lead to more reliable and accurate estimates of individual breast cancer risk. Longitudinal breast density has the potential to improve personal breast cancer risk estimation in women attending mammography screening.

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

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

Variation in second breast cancer risk after primary invasive cancer by time since primary cancer diagnosis and estrogen receptor status.

BACKGROUND: In women with previously treated breast cancer, occurrence and timing of second breast cancers have implications for surveillance. The authors examined the timing of second breast cancers by primary cancer estrogen receptor (ER) status in the Breast Cancer Surveillance Consortium. METHODS: Women who were diagnosed with American Joint Commission on Cancer stage I-III breast cancer were identified within six Breast Cancer Surveillance Consortium registries from 2000 to 2017. Characteristics collected at primary breast cancer diagnosis included demographics, ER status, and treatment. Second breast cancer events included subsequent ipsilateral or contralateral breast cancers diagnosed >6 months after primary diagnosis. The authors examined cumulative incidence and second breast cancer rates by primary cancer ER status during 1-5 versus 6-10 years after diagnosis. RESULTS: At 10 years, the cumulative second breast cancer incidence was 11.8% (95% confidence interval [CI], 10.7%-13.1%) for women with ER-negative disease and 7.5% (95% CI, 7.0%-8.0%) for those with ER-positive disease. Women with ER-negative cancer had higher second breast cancer rates than those with ER-positive cancer during the first 5 years of follow-up (16.0 per 1000 person-years [PY]; 95% CI, 14.2-17.9 per 1000 PY; vs. 7.8 per 1000 PY; 95% CI, 7.3-8.4 per 1000 PY, respectively). After 5 years, second breast cancer rates were similar for women with ER-negative versus ER-positive breast cancer (12.1 per 1000 PY; 95% CI, 9.9-14.7; vs. 9.3 per 1000 PY; 95% CI, 8.4-10.3 per 1000 PY, respectively). CONCLUSIONS: ER-negative primary breast cancers are associated with a higher risk of second breast cancers than ER-positive cancers during the first 5 years after diagnosis. Further study is needed to examine the potential benefit of more intensive surveillance targeting these women in the early postdiagnosis period.

Comparison of Mammography AI Algorithms with a Clinical Risk Model for 5-year Breast Cancer Risk Prediction: An Observational Study.

Background Although several clinical breast cancer risk models are used to guide screening and prevention, they have only moderate discrimination. Purpose To compare selected existing mammography artificial intelligence (AI) algorithms and the Breast Cancer Surveillance Consortium (BCSC) risk model for prediction of 5-year risk. Materials and Methods This retrospective case-cohort study included data in women with a negative screening mammographic examination (no visible evidence of cancer) in 2016, who were followed until 2021 at Kaiser Permanente Northern California. Women with prior breast cancer or a highly penetrant gene mutation were excluded. Of the 324 009 eligible women, a random subcohort was selected, regardless of cancer status, to which all additional patients with breast cancer were added. The index screening mammographic examination was used as input for five AI algorithms to generate continuous scores that were compared with the BCSC clinical risk score. Risk estimates for incident breast cancer 0 to 5 years after the initial mammographic examination were calculated using a time-dependent area under the receiver operating characteristic curve (AUC). Results The subcohort included 13 628 patients, of whom 193 had incident cancer. Incident cancers in eligible patients (additional 4391 of 324 009) were also included. For incident cancers at 0 to 5 years, the time-dependent AUC for BCSC was 0.61 (95% CI: 0.60, 0.62). AI algorithms had higher time-dependent AUCs than did BCSC, ranging from 0.63 to 0.67 (Bonferroni-adjusted P < .0016). Time-dependent AUCs for combined BCSC and AI models were slightly higher than AI alone (AI with BCSC time-dependent AUC range, 0.66-0.68; Bonferroni-adjusted P < .0016). Conclusion When using a negative screening examination, AI algorithms performed better than the BCSC risk model for predicting breast cancer risk at 0 to 5 years. Combined AI and BCSC models further improved prediction. © RSNA, 2023 Supplemental material is available for this article.

Strategies to Increase Cervical Cancer Screening With Mailed Human Papillomavirus Self-Sampling Kits: A Randomized Clinical Trial.

Importance: Optimal strategies for increasing cervical cancer screening may differ by patient screening history and health care setting. Mailing human papillomavirus (HPV) self-sampling kits to individuals who are overdue for screening increases adherence; however, offering self-sampling kits to screening-adherent individuals has not been evaluated in the US. Objective: To evaluate the effectiveness of direct-mail and opt-in approaches for offering HPV self-sampling kits to individuals by cervical cancer screening history (screening-adherent and currently due, overdue, or unknown). Design, Setting, and Participants: Randomized clinical trial conducted in Kaiser Permanente Washington, a US integrated health care delivery system. Individuals aged 30 to 64 years with female sex, a primary care clinician, and no hysterectomy were identified through electronic health records (EHRs) and enrolled between November 20, 2020, and January 28, 2022, with follow-up through July 29, 2022. Interventions: Individuals stratified as due (eg, at the time of randomization, these individuals have been previously screened and are due for their next screening in ≤3 months) were randomized to receive usual care (patient reminders and clinician EHR alerts [n = 3671]), education (usual care plus educational materials about screening [n = 3960]), direct mail (usual care plus educational materials and a mailed self-sampling kit [n = 1482]), or to opt in (usual care plus educational materials and the option to request a kit [n = 3956]). Individuals who were overdue for screening were randomized to receive usual care (n = 5488), education (n = 1408), or direct mail (n = 1415). Individuals with unknown history for screening were randomized to receive usual care (n = 2983), education (n = 3486), or to opt in (n = 3506). Main Outcomes and Measures: The primary outcome was screening completion within 6 months. Primary analyses compared direct-mail or opt-in participants with individuals randomized to the education group. Results: The intention-to-treat analyses included 31 355 randomized individuals (mean [SD] age, 45.9 [10.4] years). Among those who were due for screening, compared with receiving education alone (1885 [47.6%]), screening completion was 14.1% (95% CI, 11.2%-16.9%) higher in the direct-mail group (914 [61.7%]) and 3.5% (95% CI, 1.2%-5.7%) higher in the opt-in group (2020 [51.1%]). Among individuals who were overdue, screening completion was 16.9% (95% CI, 13.8%-20.0%) higher in the direct-mail group (505 [35.7%]) compared with education alone (264 [18.8%]). Among those with unknown history, screening was 2.2% (95% CI, 0.5%-3.9%) higher in the opt-in group (634 [18.1%]) compared with education alone (555 [15.9%]). Conclusions and Relevance: Within a US health care system, direct-mail self-sampling increased cervical cancer screening by more than 14% in individuals who were due or overdue for cervical cancer screening. The opt-in approach minimally increased screening. To increase screening adherence, systems implementing HPV self-sampling should prioritize direct-mail outreach for individuals who are due or overdue for screening. For individuals with unknown screening history, testing alternative outreach approaches and additional efforts to document screening history are warranted. Trial Registration: ClinicalTrials.gov Identifier: NCT04679675.

Treatment-related thoracic soft tissue sarcomas in US breast cancer survivors: a retrospective cohort study.

BACKGROUND: Soft tissue sarcoma is a rare but serious side-effect of radiotherapy to treat breast cancer, and rates are increasing in the USA. We evaluated potential co-factors in two complimentary cohorts of US breast cancer survivors. METHODS: In this retrospective cohort study, we sourced data from the Kaiser Permanente (KP) cohort and the Surveillance, Epidemiology, and End Results (SEER) 13 registries cohort, both in the USA. The KP cohort included 15 940 women diagnosed with breast cancer from Jan 1, 1990, to Dec 31, 2016, in KP Colorado, KP Northwest (which serves Oregon and Southwest Washington state), or KP Washington, with detailed treatment data and comorbidities (including hypertension and diabetes at or before breast cancer diagnosis) from electronic medical records. The SEER cohort included 457 300 women diagnosed with breast cancer from Jan 1, 1992, to Dec 31, 2016, within the 13 SEER registries across the USA, with initial treatment data (yes vs no or unknown). Eligibility criteria in both cohorts were female breast cancer survivors (stage I-III) aged 20-84 years at diagnosis who had breast cancer surgery, and had survived at least 1 year after breast cancer diagnosis. The outcome of interest was any second thoracic soft tissue sarcoma (angiosarcomas and other subtypes) that developed at least 1 year after breast cancer diagnosis. Risk factors for thoracic soft tissue sarcoma were assessed using multivariable Poisson regression models. FINDINGS: In the KP cohort, median follow-up was 9·3 years (IQR 5·7-13·9) and 19 (0·1%) of 15 940 eligible, evaluable women developed a thoracic soft tissue sarcoma (11 angiosarcomas, eight other subtypes). Most (94·7%; 18 of 19) thoracic soft tissue sarcomas occurred in women treated with radiotherapy; thus, radiotherapy was associated with a significantly increased risk of developing a thoracic soft tissue sarcoma (relative risk [RR] 8·1 [95% CI 1·1-60·4]; p=0·0052), but there was no association with prescribed dose, fractionation, or boost. The RR of angiosarcoma after anthracyclines was 3·6 (95% CI 1·0-13·3; p=0·058). Alkylating agents were associated with an increased risk of developing other sarcomas (RR 7·7 [95% CI 1·2-150·8]; p=0·026). History of hypertension (RR 4·8 [95% CI 1·3-17·6]; p=0·017) and diabetes (5·3 [1·4-20·8]; p=0·036) were each associated with around a five-times increased risk of angiosarcoma. In the SEER cohort, 430 (0·1%) of 457 300 patients had subsequent thoracic soft tissue sarcomas (268 angiosarcomas and 162 other subtypes) after a median follow-up of 8·3 years (IQR 4·3-13·9). Most (77·9%; 335 of 430) cases occurred after radiotherapy; thus, radiotherapy was associated with a significantly increased risk of developing a thoracic soft tissue sarcoma (RR 3·0 [95% CI 2·4-3·8]; p<0·0001) and, for angiosarcomas, the RR for breast-conserving surgery plus radiotherapy versus mastectomy plus radiotherapy was 1·9 (1·1-3·3; p=0·012). By 10 years after radiotherapy, the cumulative incidence of thoracic soft tissue sarcoma was 0·21% (95% CI 0·12-0·34) in the KP cohort and 0·15% (95% CI 0·13-0·17) in SEER. INTERPRETATION: Radiotherapy was the strongest risk factor for thoracic soft tissue sarcoma in both cohorts. This finding, along with the novel findings for diabetes and hypertension as potential risk factors for angiosarcomas, warrant further investigation as potential targets for prevention strategies and increased surveillance. FUNDING: US National Cancer Institute and National Institutes of Health.

Preoperative MRI in breast cancer: effect of breast density on biopsy rate and yield.

PURPOSE: Preoperative breast MRI is used to evaluate for additional cancer and extent of disease for newly diagnosed breast cancer, yet benefits and harms of preoperative MRI are not well-documented. We examined whether preoperative MRI yields additional biopsy and cancer detection by extent of breast density. METHODS: We followed women in the Breast Cancer Surveillance Consortium with an incident breast cancer diagnosed from 2005 to 2017. We quantified breast biopsies and cancers detected within 6 months of diagnosis by preoperative breast MRI receipt, overall and by breast density, accounting for MRI selection bias using inverse probability weighted logistic regression. RESULTS: Among 19,324 women with newly diagnosed breast cancer, 28% had preoperative MRI, 11% additional biopsy, and 5% additional cancer detected. Four times as many women with preoperative MRI underwent additional biopsy compared to women without MRI (22.6% v. 5.1%). Additional biopsy rates with preoperative MRI increased with increasing breast density (27.4% for extremely dense compared to 16.2% for almost entirely fatty breasts). Rates of additional cancer detection were almost four times higher for women with v. without MRI (9.9% v. 2.6%). Conditional on additional biopsy, age-adjusted rates of additional cancer detection were lowest among women with extremely dense breasts, regardless of imaging modality (with MRI: 35.0%; 95% CI 27.0-43.0%; without MRI: 45.1%; 95% CI 32.6-57.5%). CONCLUSION: For women with dense breasts, preoperative MRI was associated with much higher biopsy rates, without concomitant higher cancer detection. Preoperative MRI may be considered for some women, but selecting women based on breast density is not supported by evidence. TRIAL REGISTRATION: ClinicalTrials.gov: NCT02980848; registered 2017.

Endocrine therapy initiation among women with stage I-III invasive, hormone receptor-positive breast cancer from 2001-2016.

PURPOSE: This retrospective cohort study examined patterns of endocrine therapy initiation over time and by demographic, tumor, and treatment characteristics. METHODS: We included 7777 women from three U.S. integrated healthcare systems diagnosed with incident stage I-III hormone receptor-positive breast cancer between 2001 and 2016. We extracted endocrine therapy from pharmacy dispensings, defining initiation as dispensings within 12 months of diagnosis. Demographic, tumor, and treatment characteristics were collected from electronic health records. Using generalized linear models with a log link and Poisson distribution, we estimated initiation of any endocrine therapy, tamoxifen, and aromatase inhibitors (AI) over time with relative risks (RR) and 95% confidence intervals (CI) adjusted for age, tumor characteristics, diagnosis year, other treatment, and study site. RESULTS: Among women aged 20+ (mean 62 years), 6329 (81.4%) initiated any endocrine therapy, and 1448 (18.6%) did not initiate endocrine therapy. Tamoxifen initiation declined from 67 to 15% between 2001 and 2016. AI initiation increased from 6 to 69% between 2001 and 2016 in women aged ≥ 55 years. The proportion of women who did not initiate endocrine therapy decreased from 19 to 12% between 2002 and 2014 then increased to 17% by 2016. After adjustment, women least likely to initiate endocrine therapy were older (RR = 0.81, 95% CI 0.77-0.85 for age 75+ vs. 55-64), Black (RR = 0.93, 95% CI 0.87-1.00 vs. white), and had stage I disease (RR = 0.88, 95% CI 0.85-0.91 vs. stage III). CONCLUSIONS: Despite an increase in AI use over time, at least one in six eligible women did not initiate endocrine therapy, highlighting opportunities for improving endocrine therapy uptake in breast cancer survivors.

Decision quality and regret with treatment decisions in women with breast cancer: Pre-operative breast MRI and breast density.

PURPOSE: We evaluated self-report of decision quality and regret with breast cancer surgical treatment by pre-operative breast MRI use in women recently diagnosed with breast cancer. METHODS: We conducted a survey with 957 women aged 18 + with stage 0-III breast cancer identified in the Breast Cancer Surveillance Consortium. Participants self-reported receipt of pre-operative breast MRI. Primary outcomes were process measures in the Breast Cancer Surgery Decision Quality Instrument (BCS-DQI) (continuous outcome) and Decision Regret Scale (dichotomized outcome as any/none). Generalized estimating equations with linear and logit link were used to estimate adjusted associations between breast MRI and primary outcomes. All analyses were also stratified by breast density. RESULTS: Survey participation rate was 27.9% (957/3430). Study population was primarily > 60 years, White, college educated, and diagnosed with early-stage breast cancer. Pre-operative breast MRI was reported in 46% of women. A higher proportion of women who were younger age (< 50 years), commercially insured, and self-detected their breast cancer reported pre-operative breast MRI use. In adjusted analysis, pre-operative breast MRI use compared with no use was associated with a small but statistically significantly higher decision quality scores (69.5 vs 64.7, p-value = 0.043). Decision regret did not significantly differ in women who reported pre-operative breast MRI use compared with no use (54.2% v. 48.7%, respectively, p-value = 0.11). Study results did not vary when stratified by breast density for either primary outcome. CONCLUSIONS AND RELEVANCE: Breast MRI use in the diagnostic work-up of breast cancer does not negatively alter women's perceptions of surgical treatment decisions in early survivorship. CLINICAL TRIALS REGISTRATION NUMBER: NCT03029286.

Breast Biopsy Recommendations and Breast Cancers Diagnosed during the COVID-19 Pandemic.

Background The COVID-19 pandemic reduced mammography use, potentially delaying breast cancer diagnoses. Purpose To examine breast biopsy recommendations and breast cancers diagnosed before and during the COVID-19 pandemic by mode of detection (screen detected vs symptomatic) and women's characteristics. Materials and Methods In this secondary analysis of prospectively collected data, monthly breast biopsy recommendations after mammography, US, or both with subsequent biopsy performed were examined from 66 facilities of the Breast Cancer Surveillance Consortium between January 2019 and September 2020. The number of monthly and cumulative biopsies recommended and performed and the number of subsequent cancers diagnosed during the pandemic period (March 2020 to September 2020) were compared with data from the prepandemic period using Wald χ2 tests. Analyses were stratified by mode of detection and race or ethnicity. Results From January 2019 to September 2020, 17 728 biopsies were recommended and performed, with 6009 cancers diagnosed. From March to September 2020, there were substantially fewer breast biopsy recommendations with cancer diagnoses when compared with the same period in 2019 (1650 recommendations in 2020 vs 2171 recommendations in 2019 [24% fewer], P < .001), predominantly due to fewer screen-detected cancers (722 cancers in 2020 vs 1169 cancers in 2019 [38% fewer], P < .001) versus symptomatic cancers (895 cancers in 2020 vs 965 cancers in 2019 [7% fewer], P = .27). The decrease in cancer diagnoses was largest in Asian (67 diagnoses in 2020 vs 142 diagnoses in 2019 [53% fewer], P = .06) and Hispanic (82 diagnoses in 2020 vs 145 diagnoses in 2019 [43% fewer], P = .13) women, followed by Black women (210 diagnoses in 2020 vs 287 diagnoses in 2019 [27% fewer], P = .21). The decrease was smallest in non-Hispanic White women (1128 diagnoses in 2020 vs 1357 diagnoses in 2019 [17% fewer], P = .09). Conclusion There were substantially fewer breast biopsies with cancer diagnoses during the COVID-19 pandemic from March to September 2020 compared with the same period in 2019, with Asian and Hispanic women experiencing the largest declines, followed by Black women. © RSNA, 2022 Online supplemental material is available for this article. See also the editorial by Heller in this issue.

Accuracy of tumor registry versus pharmacy dispensings for breast cancer adjuvant endocrine therapy.

PURPOSE: Accounting for endocrine therapy use for breast cancer treatment is important for studies of survivorship. We evaluated the accuracy of Surveillance, Epidemiology, and End Results (SEER) breast cancer endocrine therapy data compared with pharmacy dispensings from an integrated health system. METHODS: We included women with non-metastatic hormone receptor positive primary breast cancer diagnosed between 1995 and 2017 enrolled in Kaiser Permanente Washington, linking their data with SEER. We used pharmacy dispensings for endocrine therapy within one year following diagnosis as our reference standard. We calculated kappa (concordance), positive predictive value (PPV), and negative predictive values (NPV) overall and stratified by woman and tumor characteristics of interest. RESULTS: Of 5,055 women, mean age at diagnosis was 62 years (interquartile range = 53-71); 53% had localized stage, 56% received lumpectomy with radiation, and 31% received chemotherapy. SEER data alone identified 67% of women as having received endocrine therapy; this increased to 75% with pharmacy dispensings. SEER's concordance with pharmacy dispensings was 0.68 (PPV = 91%; NPV = 76%). PPV did not vary by tumor or women characteristics; however, NPV declined with younger age at diagnosis (64% in < 45 years vs. 86% in 75+ years), increasing tumor stage (49% in regional stage vs. 91% in DCIS), and chemotherapy treatment (41% in those with chemotherapy vs. 83% in those without chemotherapy). CONCLUSION: Pharmacy dispensings enable more complete endocrine therapy capture, particularly in women with more advanced tumors or who receive chemotherapy. We determined woman, tumor, and treatment characteristics that contribute to underascertainment of endocrine therapy use in tumor registries.

The influence of treatment on hormone receptor subgroups and breast cancer-specific mortality within US integrated healthcare systems.

PURPOSE: Estrogen receptor (ER) + /progesterone receptor (PR) - or ER-/PR + breast cancer prognosis has not been well-described outside of clinical trials. We evaluated the relationship between ER/PR (ER + /PR-, ER-/PR + , ER + /PR + , ER-/PR-) subgroups and breast cancer-specific mortality within a general community setting in the US. METHODS: A Retrospective cohort of 11,737 women diagnosed with breast cancer between 1990 and 2016 within US integrated healthcare systems (median follow-up = 7 years; 1,104 breast cancer-specific deaths) were included in this analysis. Cox proportional hazards models were used to estimate hazard ratios (HR) and 95% confidence intervals (CI) adjusting for site, demographic and clinicopathological characteristics, and treatment (surgery/radiotherapy, chemotherapy, endocrine therapy). RESULTS: Breast cancer-specific mortality was higher for those with ER + /PR- (n = 1,233) compared with ER + /PR + tumors (n = 8,439) before (HR = 1.43; 95% CI = 1.17-1.75) and after treatment adjustment (HR = 1.58; 95% CI = 1.27-1.97). ER + /PR- breast cancer-specific mortality remained higher than ER + /PR + tumors when stratified by treatment received. Breast cancer-specific mortality was similar in ER-/PR + (n = 161) compared with ER + /PR + tumors. CONCLUSION: Our findings suggest that ER + /PR- tumors may have worse breast cancer-specific mortality than ER + /PR + tumors in a community setting.

Does mailing unsolicited HPV self-sampling kits to women overdue for cervical cancer screening impact uptake of other preventive health services in a United States integrated delivery system?

Women overdue for cervical cancer screening often have other preventive care gaps. We examined whether mailing unsolicited human papillomavirus (HPV) self-sampling kits to increase cervical cancer screening impacted receipt of other preventive services women were due for: mammography, colorectal cancer (CRC) screening, influenza vaccination, depression screening, and diabetic HbA1c monitoring. From 2014 to 2016, 16,590 underscreened women were randomized to receive a mailed kit or usual care Pap reminders within Kaiser Permanente Washington. We used logistic regression to estimate odds ratios (ORs) of preventive services receipt within 12-months between the intervention vs. control arms, and within the intervention arm (comparing those returning a kit vs. attending Pap vs. nothing), adjusting models for demographic variables. There were no significant between-arm differences in uptake of any of the preventive services: intervention vs. control: mammography OR = 1.01 (95% confidence interval:0.88-1.17), CRC screening OR = 0.98 (0.86-1.13), influenza vaccination OR = 0.99 (0.92-1.06), depression screening OR = 1.07 (0.99-1.16), HbA1c OR = 0.84 (0.62-1.13). Within the intervention arm, preventive services uptake was higher in women who completed cervical cancer screening vs. did not, with stronger effects for women who attended Pap: Pap vs. nothing: mammography OR = 11.81 (8.11-17.19), CRC screening OR = 7.31 (5.57-9.58), influenza vaccination OR = 2.06 (1.82-2.32), depression screening OR = 1.79 (1.57-2.05), HbA1c OR = 3.35 (1.49-7.52); kit vs. nothing: mammography OR = 2.26 (1.56-3.26), CRC screening OR = 5.05 (3.57-7.14), influenza vaccination OR = 1.67 (1.41-1.98), depression screening OR = 1.09 (0.89-1.33), HbA1c OR = 1.23 (0.57-2.65). Mailing HPV self-sampling kits to underscreened women did not negatively impact uptake of other preventive services. However, overall preventive service uptake was the highest among women who attended in-clinic cervical cancer screening.

Imaging Surveillance Options for Individuals With a Personal History of Breast Cancer: AJR Expert Panel Narrative Review.

Annual surveillance mammography is recommended for breast cancer survivors on the basis of observational studies and meta-analyses showing reduced breast cancer mortality and improved quality of life. However, breast cancer survivors are at higher risk of subsequent breast cancer and have a fourfold increased risk of interval breast cancers compared with individuals without a personal history of breast cancer. Supplemental surveillance modalities offer increased cancer detection compared with mammography alone, but utilization is variable, and benefits must be balanced with possible harms of false-positive findings. In this review, we describe the current state of mammographic surveillance, summarize evidence for supplemental surveillance in breast cancer survivors, and explore a risk-based approach to selecting surveillance imaging strategies. Further research identifying predictors associated with increased risk of interval second breast cancers and development of validated risk prediction tools may help physicians and patients weigh the benefits and harms of surveillance breast imaging and decide on a personalized approach to surveillance for improved breast cancer outcomes.

Association of Screening With Digital Breast Tomosynthesis vs Digital Mammography With Risk of Interval Invasive and Advanced Breast Cancer.

Importance: Digital breast tomosynthesis (DBT) was developed with the expectation of improving cancer detection in women with dense breasts. Studies are needed to evaluate interval invasive and advanced breast cancer rates, intermediary outcomes related to breast cancer mortality, by breast density and breast cancer risk. Objective: To evaluate whether DBT screening is associated with a lower likelihood of interval invasive cancer and advanced breast cancer compared with digital mammography by extent of breast density and breast cancer risk. Design, Setting, and Participants: Cohort study of 504 427 women aged 40 to 79 years who underwent 1 003 900 screening digital mammography and 375 189 screening DBT examinations from 2011 through 2018 at 44 US Breast Cancer Surveillance Consortium (BCSC) facilities with follow-up for cancer diagnoses through 2019 by linkage to state or regional cancer registries. Exposures: Breast Imaging Reporting and Data System (BI-RADS) breast density; BCSC 5-year breast cancer risk. Main Outcomes and Measures: Rates per 1000 examinations of interval invasive cancer within 12 months of screening mammography and advanced breast cancer (prognostic pathologic stage II or higher) within 12 months of screening mammography, both estimated with inverse probability weighting. Results: Among 504 427 women in the study population, the median age at time of mammography was 58 years (IQR, 50-65 years). Interval invasive cancer rates per 1000 examinations were not significantly different for DBT vs digital mammography (overall, 0.57 vs 0.61, respectively; difference, -0.04; 95% CI, -0.14 to 0.06; P = .43) or among all the 836 250 examinations with BCSC 5-year risk less than 1.67% (low to average-risk) or all the 413 061 examinations with BCSC 5-year risk of 1.67% or higher (high risk) across breast density categories. Advanced cancer rates were not significantly different for DBT vs digital mammography among women at low to average risk or at high risk with almost entirely fatty, scattered fibroglandular densities, or heterogeneously dense breasts. Advanced cancer rates per 1000 examinations were significantly lower for DBT vs digital mammography for the 3.6% of women with extremely dense breasts and at high risk of breast cancer (13 291 examinations in the DBT group and 31 300 in the digital mammography group; 0.27 vs 0.80 per 1000 examinations; difference, -0.53; 95% CI, -0.97 to -0.10) but not for women at low to average risk (10 611 examinations in the DBT group and 37 796 in the digital mammography group; 0.54 vs 0.42 per 1000 examinations; difference, 0.12; 95% CI, -0.09 to 0.32). Conclusions and Relevance: Screening with DBT vs digital mammography was not associated with a significant difference in risk of interval invasive cancer and was associated with a significantly lower risk of advanced breast cancer among the 3.6% of women with extremely dense breasts and at high risk of breast cancer. No significant difference was observed in the 96.4% of women with nondense breasts, heterogeneously dense breasts, or with extremely dense breasts not at high risk.

Digital Mammography and Breast Tomosynthesis Performance in Women with a Personal History of Breast Cancer, 2007-2016.

Background Since 2007, digital mammography and digital breast tomosynthesis (DBT) replaced screen-film mammography. Whether these technologic advances have improved diagnostic performance has, to the knowledge of the authors, not yet been established. Purpose To evaluate the performance and outcomes of surveillance mammography (digital mammography and DBT) performed from 2007 to 2016 in women with a personal history of breast cancer and compare with data from 1996 to 2007 and the performance of digital mammography screening benchmarks. Materials and Methods In this observational cohort study, five Breast Cancer Surveillance Consortium registries provided prospectively collected mammography data linked with tumor registry and pathologic outcomes. This study identified asymptomatic women with American Joint Committee on Cancer anatomic stages 0-III primary breast cancer who underwent surveillance mammography from 2007 to 2016. The primary outcome was a second breast cancer diagnosis within 1 year of mammography. Performance measures included the recall rate, cancer detection rate, interval cancer rate, positive predictive value of biopsy recommendation, sensitivity, and specificity. Results Among 32 331 women who underwent 117 971 surveillance mammographic examinations (112 269 digital mammographic examinations and 5702 DBT examinations), the mean age at initial diagnosis was 59 years ± 12 (standard deviation). Of 1418 second breast cancers diagnosed, 998 were surveillance-detected cancers and 420 were interval cancers. The recall rate was 8.8% (10 365 of 117 971; 95% CI: 8.6%, 9.0%), the cancer detection rate was 8.5 per 1000 examinations (998 of 117 971; 95% CI: 8.0, 9.0), the interval cancer rate was 3.6 per 1000 examinations (420 of 117 971; 95% CI: 3.2, 3.9), the positive predictive value of biopsy recommendation was 31.0% (998 of 3220; 95% CI: 29.4%, 32.7%), the sensitivity was 70.4% (998 of 1418; 95% CI: 67.9%, 72.7%), and the specificity was 98.1% (114 331 of 116 553; 95% CI: 98.0%, 98.2%). Compared with previously published studies, interval cancer rate was comparable with rates from 1996 to 2007 in women with a personal history of breast cancer and was higher than the published digital mammography screening benchmarks. Conclusion In transitioning from screen-film to digital mammography and digital breast tomosynthesis, surveillance mammography performance demonstrated minimal improvement over time and remained inferior to the performance of screening mammography benchmarks. © RSNA, 2021 Online supplemental material is available for this article. See also the editorial by Moy and Gao in this issue.

Out of reach? Correlates of cervical cancer underscreening in women with varying levels of healthcare interactions in a United States integrated delivery system.

One in five U.S. women with health insurance are underscreened for cervical cancer. We sought to identify whether underscreening correlates differed among women with different levels of health care interaction. Among women age 30-64 years who were members of an integrated U.S. health system, we used 2014-2015 electronic health record data to identify underscreened cases (≥3.4 years since last Papanicolaou (Pap) test, n=3352) and screening-adherent controls (<3.4 years since last Pap test, n=45,359) and extracted data on potential underscreening correlates (demographics, health history, and healthcare utilization). We calculated the odds of underscreening in the total population and by subgroups defined by healthcare visits and online health portal usage in the prior 12 months. Underscreening was associated with older age (50-64 vs. 30-39; odds ratio (OR)=1.6; 95%CI=1.4-1.8), current tobacco use (vs. never use; OR=2.1; 95%CI=1.8-2.2), higher BMI (≥35 kg/m2 vs <25 kg/m2, OR=2.0; 95%CI=1.8-2.3), screening non-adherence for colorectal cancer (OR=5.1; 95%CI=4.6-5.7) and breast cancer (OR=8.1, 95%CI=7.2-9.0), and having no recent visit with their primary care provider (PCP) nor recent health portal use (vs. recent PCP visit and portal use; OR=8.4, 95%CI=7.6-9.4). Underscreening correlates were similar between the total study population and within all healthcare interaction groups. Interaction with the healthcare system is associated with lower odds of underscreening, but sociodemographic and health status correlates are similar regardless of primary care visits or online portal use. These data support the need for additional interventions to reach insured women who remain underscreened for cervical cancer.

Women's considerations and experiences for breast cancer screening and surveillance during the COVID-19 pandemic in the United States: A focus group study.

The COVID-19 pandemic resulted in numerous changes in delivery of healthcare services, including breast cancer screening and surveillance. Although facilities have implemented a number of strategies to provide services, women's thoughts and experiences related to breast cancer screening and surveillance during a pandemic are not well known. This focus group study with women across seven states recruited through the Breast Cancer Surveillance Consortium aims to remedy this gap in information. Thirty women ranging in age from 31 to 69 participated in five virtual focus groups, eight of whom had prior breast cancer. The first three focus groups covered a range of topics related to screening and surveillance during the pandemic while the last two groups covered experiences and then a review of sample communications to women about screening and surveillance during the pandemic to obtain reactions and recommendations. More than half of the women had screening or surveillance during the pandemic. Coding and analyses resulted in nine themes in three topic areas: decision factors, screening experiences, and preferred communications. Themes included weighing the risks of COVID-19 versus cancer; feelings that screening and surveillance were mostly safe but barriers may be heightened; feeling safe when undergoing screening but receiving a range of pandemic-specific communications from none to a lot; and wanting communications that are personalized, clear and concise. Based on these findings, providers and facilities should assure women of pandemic safety measures, review methods and content of communications, and assess for barriers to screening that may be amplified during the pandemic, including anxiety and access.

Prioritizing breast imaging services during the COVID pandemic: A survey of breast imaging facilities within the Breast Cancer Surveillance Consortium.

The COVID-19 pandemic disrupted breast cancer screening and diagnostic imaging in the United States. We sought to evaluate how medical facilities prioritized breast imaging services during periods of reduced capacity or upon re-opening after closures. In fall 2020, we surveyed 77 breast imaging facilities within the Breast Cancer Surveillance Consortium in the United States. The survey ascertained the pandemic's impact on clinical practices during March-September 2020. Nearly all facilities (97%) reported closing or operating at reduced capacity at some point during this period. All facilities were open by August 2020, though 14% were still operating at reduced capacity in September 2020. During periods of re-opening or reduced capacity, 93% of facilities reported prioritizing diagnostic breast imaging over breast cancer screening. For diagnostic imaging, facilities prioritized based on rescheduling canceled appointments (89%), specific indication for diagnostic imaging (89%), patient demand (84%), individual characteristics and risk factors (77%), and time since last imaging examination (72%). For screening mammography, facilities prioritized based on rescheduled cancelations (96%), patient demand (83%), individual characteristics and risk factors (73%), and time since last mammogram (71%). For biopsy services, more than 90% of facilities reported prioritization based on rescheduling of canceled exams, patient demand, patient characteristics and risk factors and level of suspicion on imaging. The observed patterns from this large and geographically diverse sample of facilities in the United States indicate that multiple factors were commonly used to prioritize breast imaging services during periods of reduced capacity.

Knowledge and Perception of Breast Density, Screening Mammography, and Supplemental Screening: in Search of "Informed".

BACKGROUND: As of 2019, 37 US states have breast density notification laws. No qualitative study to date has examined women's perspectives about breast density in general or by states with and without notification laws. OBJECTIVE: Explore women's knowledge and perceptions of breast density and experiences of breast cancer screening across three states with and without notification laws. DESIGN: Qualitative research design using four focus groups conducted in 2017. PARTICIPANTS: Forty-seven women who had a recent normal mammogram and dense breasts in registry data obtained through the Breast Cancer Surveillance Consortium. APPROACH: Focus groups were 90 min, audio recorded, and transcribed for analysis. Data were analyzed using mixed deductive and inductive coding. KEY RESULTS: Women reported variable knowledge levels of personal breast density and breast density in general, even among women living in states with a notification law. A number of women were aware of the difficulty of detecting cancer with dense breasts, but only one knew that density increased breast cancer risk. Across all states, very few women reported receiving information about breast density during healthcare visits beyond being encouraged to get supplemental imaging or to pay for new mammography technology (i.e., breast tomosynthesis). Women offered more imaging or different technology held strong convictions that these were "better," even though knowledge of differences, effectiveness, or harms across technologies seemed limited. Women from all states expressed a strong desire for more information about breast density. CONCLUSIONS: More research needs to be done to understand how the medical community can best assist women in making informed decisions related to breast density, mammography, and supplemental screening. Options to explore include improved breast density notifications and education materials about breast density, continued development of personalized risk information tools, strategies for providers to discuss evidence and options based on risk stratification, and shared decision-making.