Rate Of Invasive Breast Cancer Research Articles

Hormone replacement therapy and breast cancer incidence in Korean women

ObjectivesAfter the 2002 Women's Health Initiative (WHI) study, the global use of menopausal hormone therapy (MHT) declined, and despite subsequent studies indicating a low risk of breast cancer, concerns about MHT usage persist. We examined the relationship between changes in MHT use and changes in the incidence of breast cancer from 2002 to 2020 in South Korea. Study designThis study used tumor registry information from 2002 to 2020 from the Korean Statistical Information Service and analyzed the incidence rate of invasive breast cancer in women, who were divided into two age groups: <50 and >50 years. The numbers of MHT prescriptions in Korea between 2002 and 2020 was determined from pharmacy data. ResultsThe incidence of breast cancer per 100,000 women in South Korea increased from 34.3 in 2002 to 96.4 in 2020. Breast cancer incidence rates increased annually in both groups of women (those aged under and over 50 years), with no significant difference between the two (p = 0.614). Prescriptions for estrogen therapy (ET) in 2020 were 52.7 % lower than those in 2002. Prescriptions for estrogen-progesterone therapy (EPT) decreased by 27.9 % over the same period. Conversely, tibolone prescriptions, which had initially decreased by 25.4 % in 2004, subsequently showed a steady increase and were 93.6 % higher in 2020 than in 2002. ConclusionThe incidence of breast cancer increased annually in Korean women of all ages; however, the use of ET and EPT for MHT has declined since 2002, particularly the use of EPT after 2010. MHT, especially EPT, did not significantly increase the incidence of breast cancer in Korean women.

The prognostic potential of mammographic growth rate of invasive breast cancer in the Nijmegen breast cancer screening cohort.

Insight into the aggressiveness of potential breast cancers found in screening may optimize recall decisions. Specific growth rate (SGR), measured on mammograms, may provide valuable prognostic information. This study addresses the association of SGR with prognostic factors and overall survival in patients with invasive carcinoma of no special type (NST) from a screened population. In this historic cohort study, 293 women with NST were identified from all participants in the Nijmegen screening program (2003-2007). Information on clinicopathological factors was retrieved from patient files and follow-up on vital status through municipalities. On consecutive mammograms, tumor volumes were estimated. After comparing five growth functions, SGR was calculated using the best-fitting function. Regression and multivariable survival analyses described associations between SGR and prognostic factors as well as overall survival. Each one standard deviation increase in SGR was associated with an increase in the Nottingham prognostic index by 0.34 [95% confidence interval (CI): 0.21-0.46]. Each one standard deviation increase in SGR increased the odds of a tumor with an unfavorable subtype (based on histologic grade and hormone receptors; odds ratio 2.14 [95% CI: 1.45-3.15]) and increased the odds of diagnosis as an interval cancer (versus screen-detected; odds ratio 1.57 [95% CI: 1.20-2.06]). After a median of 12.4 years of follow-up, 78 deaths occurred. SGR was not associated with overall survival (hazard ratio 1.12 [95% CI: 0.87-1.43]). SGR may indicate prognostically relevant differences in tumor aggressiveness if serial mammograms are available. A potential association with cause-specific survival could not be determined and is of interest for future research.

Invasive breast cancer and breast cancer death after non-screen detected ductal carcinoma in situ from 1990 to 2018 in England: population based cohort study

ObjectivesTo evaluate the long term risks of invasive breast cancer and death related to breast cancer after non-screen detected ductal carcinoma in situ. Risks for women in the general population...

Abstract IA020: After DCIS surgery, what next? The prevention of future breast events

Abstract Following surgical resection of DCIS, the next priority is to prevent future occurrence of invasive breast cancer (IBR). The probability of this can range from 1.5% annually to 0.2% annually, depending on age at diagnosis and a number of lesion and treatment related factors. Large clinical trials over three decades have demonstrated the efficacy of both breast radiotherapy (RT) and endocrine therapy (ET) in the prevention of subsequent IBR and DCIS (ipsilateral only for RT and contralateral as well for ET). Of these, RT is more widely used and accepted than ET, which has low uptake due concerns regarding adverse effects, and prevents only hormone receptor positive breast cancer; and. For women and their physicians, decisions regarding use of one, both, or neither of these modalities must consider both the benefits and the burdens of each. Recently updated 10-year results of RTOG 9804 show that even for low-risk DCIS, the 15-year cumulative incidence of new events was more than halved by the use of RT (7.1% versus 15.1%, P = .0007; HR = 0.36; 95% CI, 0.20 to 0.66). On multivariable analysis, only radiotherapy and tamoxifen use (HR = 0.45; 95% CI, 0.25 to 0.78; P = .0047) were associated with reduced IBR rates. Radiotherapy decisions have been aided recently by molecular assays which provide good prognostic stratification, and potentially also predictive information regarding RT benefits; these are entering clinical practice although further refinement and validation is needed. Medical therapy protects both breasts against further events, but Improvements are clearly needed, to extend the range of preventive efficacy to hormone insensitive disease, and to improve the tolerability of existing therapies. The value of identifying new agents that are effective and tolerable in the DCIS setting where the population is healthy, with long life expectancy, will likely be extendable to the larger high risk population. Therefore, DCIS provides an excellent opportunity to test new approaches to breast cancer prevention. Recent innovative attempts to improve medical therapy have focused on increasing the tolerability of known effective agents through dosing modifications (low dose tamoxifen and intermittent exemestane), and alternate delivery approaches (transdermal 4-hydroxytamoxifen). Encouraging data regarding neoadjuvant therapy has been reported from a 6-month treatment with letrozole. Strategies targeting HER-2 (expressed in a high frequency of DCIS lesions) include a trial of radiosensitization with trastuzumab, a window trial of lapatinib, and several vaccine-based approaches. Presurgical window trials have been initiated with interventions that range from palbociclib intralesional pembrolizumab. The search for new strategies that will prevent additional breast events in women diagnosed with DCIS continues will be complemented by work on improving acceptance and adherence to proven interventions. Together, these efforts will benefit the broader population of women at increased risk of breast cancer. Citation Format: Seema A. Khan. After DCIS surgery, what next? The prevention of future breast events [abstract]. In: Proceedings of the AACR Special Conference on Rethinking DCIS: An Opportunity for Prevention?; 2022 Sep 8-11; Philadelphia, PA. Philadelphia (PA): AACR; Can Prev Res 2022;15(12 Suppl_1): Abstract nr IA020.

Accuracy and Utility of Preoperative Ultrasound-Guided Axillary Lymph Node Biopsy for Invasive Breast Cancer: A Systematic Review and Meta-Analysis.

Background With the acceleration of the pace of life and work, the incidence rate of invasive breast cancer is getting higher and higher, and early diagnosis is very important. This study screened and analyzed the published literature on ultrasound-guided biopsy of invasive breast cancer and obtained the accuracy and practicality of preoperative biopsy. Method The four databases were screened for the literature. There was no requirement for the start date of retrieval, and the deadline was July 2, 2022. Two researchers screened the literature, respectively, and included the literature on preoperative ultrasound-guided biopsy and intraoperative and postoperative pathological diagnosis of invasive breast cancer. The diagnostic data included in the literature were extracted and meta-analyzed with RevMan 5.4 software, and the bias risk map, forest map, and summary receiver operating characteristic curves (SROC) were drawn. Results The included 19 studies involved about 18668 patients with invasive breast cancer. The degree of bias of the included literature is low. The distribution range of true positive, false positive, true negative, and false negative in the forest map is large, which may be related to the large difference in the number of patients in each study. Most studies in the SROC curve are at the upper left, indicating that the accuracy of ultrasound-guided axillary biopsy is very high. Conclusion For invasive breast cancer, preoperative ultrasound-guided biopsy can accurately predict staging and grading of breast cancer, which has important reference value for surgery and follow-up treatment.

Digital breast tomosynthesis plus synthesised mammography versus digital screening mammography for the detection of invasive breast cancer (TOSYMA): a multicentre, open-label, randomised, controlled, superiority trial.

Two dimensional (2D) full-field digital mammography is the current standard of breast cancer screening. Digital breast tomosynthesis generates pseudo-three dimensional datasets of the breast from which synthesised 2D (s2D) mammograms can be reconstructed. This innovative approach reduces the likelihood of overlapping breast tissues that can conceal features of malignancy. We aimed to compare digital breast tomosynthesis plus s2D mammography with digital screening mammography for the detection of invasive breast cancer. TOSYMA was a randomised, open-label, superiority trial done at 17 screening units in two federal states of Germany. Eligible participants were women aged 50-69 years who had been invited to participate in a population-wide, quality-controlled mammography screening programme. Women were randomly assigned (1:1) to digital breast tomosynthesis plus s2D mammography or digital mammography alone using block randomisation (block size of 32), stratified by site. The primary endpoints were the detection rate of invasive breast cancer and invasive interval cancer rate at 24 months, analysed in the modified full analysis set, which included all randomly assigned participants who underwent either type of screening examination. Ten examinations, corresponding to a second study participation, were excluded. Analyses were done according to the intention-to-treat principle. Interval cancer rates will be reported in the follow-up study. Safety was assessed in the as-treated population, which included all participants who were randomly assigned. This trial is registered with ClinicalTrials.gov, NCT03377036, and is closed to accrual. Between July 5, 2018, and Dec 30, 2020, 99 689 women were randomly assigned to digital breast tomosynthesis plus s2D mammography (n=49 804) or digital mammography (n=49 830). Invasive breast cancers were detected in 354 of 49 715 women with evaluable primary endpoint data in the digital breast tomosynthesis plus s2D group (detection rate 7·1 cases per 1000 women screened) and in 240 of 49 762 women in the digital mammography group (4·8 cases per 1000 women screened; odds ratio 1·48 [95% CI 1·25-1·75]; p<0·0001). Adverse events and device deficiencies were rare (six adverse events in each group; 23 device deficiencies in the digital breast tomosynthesis plus s2D group vs five device deficiencies in the digital mammography group) and no serious adverse events were reported. The results from this study indicate that the detection rate for invasive breast cancer was significantly higher with digital breast tomosynthesis plus s2D mammography than digital mammography alone. Evaluation of interval cancer rates in the follow-up study will further help to investigate incremental long-term benefits of digital breast tomosynthesis screening. Deutsche Forschungsgemeinschaft (German Research Foundation).

Hormone-Replacement Therapy and Its Association with Breast Cancer Subtypes: A Large Retrospective Cohort Study.

PurposeThe study examined trends in breast cancer incidence, mammography testing rates, hormone-replacement therapy (HRT) use and breast cancer subtypes in a large Israeli health maintenance organization during 2000–2014.MethodsAnnual rates of mammography tests and HRTs use were analyzed in women age ≥45. Annual incidence rates of breast cancer were analyzed in women age ≥20. Estimated annual percentage changes were used to test changes in incidence rates. Invasive breast cancer subtypes were approximated by treatments received. We compared annual rates and duration of HRTs use between women diagnosed with breast cancer and those who were not, as well as HRT use between subtypes of invasive breast cancer.ResultsWe identified 14,092 breast cancer cases (88% invasive, 12% in situ). The age-adjusted incidence rate of invasive breast cancer peaked in 2005, consistent with increased mammography screening that year, and decreased thereafter. HRT use decreased from 13.2% in 2002 to 4.6% in 2014. The subtypes distribution of 7771 patients diagnosed with invasive breast cancer during 2007–2014 was: luminal A and B without HER2 over-expression (HR+/HER2-), 69.7%; Luminal B with HER2 over-expression (HR+/HER2+), 8.9%; Hormone receptor-negative HER2 enriched (HR-/HER2+), 5.4%; triple negative (HR-/HER2-), 10.0%; unknown, 6.0%. Overall, in women age ≥45 diagnosed with invasive breast cancer, 76–86% did not have HRT exposure vs 14–24% who were current (within 1 year before the breast cancer diagnosis), recent (within 2–5 years), or past users (>5 years). Current/recent HRT use was statistically significantly higher in luminal vs non-luminal/unknown breast cancer subtypes (13.9% vs 8.9%, respectively; p < 0.001).ConclusionOur results show a decrease in breast cancer incidence that parallels the global and local decrease in HRT use. Yet, our results imply that current/recent HRT exposure may contribute to the incidence of luminal breast cancer tumors in particular. The magnitude of the effect supports findings from population-based studies.

Clinical performance progress of BREAST participants: the impact of test-set participation

To investigate if positive changes in the clinical performance of radiologists are associated with reading mammographic test sets. This study investigated the clinical audit history for a cohort of 39 participants in the BreastScreen Reader Assessment Strategy who have read for BreastScreen New South Wales in the period between 2010 and 2018, inclusively. Based on the year in which each radiologist completed his or her first test set, data of multiple clinical audit metrics from two calendar years before test-set reading were compared against similar data from three different periods after test-set completion. The same process was repeated after dividing radiologists into two subgroups based on their median screen-reading volume (3,688), to test if experience is a determinant of post-test set performance. On average, radiologists showed significant improvements (p<0.05) in the recall rate for subsequent screening rounds, in positive predictive value 1 (PPV1), and in specificity. When dividing radiologists based on their average annual reading volume, radiologists with higher reading numbers demonstrated similar significant improvements in the recall rate and in PPV1. In addition, they showed significant improvements in the detection rates of invasive breast cancer and ductal carcinoma in situ (DCIS). In contrast, the radiologists with lower reading volume indicated significant changes in the recall rate and in PPV1, both accruing in one of the three compared periods. Mammographic test-set participants improve over time in identifying normal breast screens and detecting breast cancer in association with reading higher volumes of breast screening cases.

906Can mammographic density add value to the Gail model in risk-stratifying women in BreastScreen Australia?

Abstract Background There is significant interest in personalised, risk-based breast cancer screening. This requires high quality risk assessment. The ‘Gail model’ risk assessment tool has been validated on over 40,000 BreastScreen Australia participants. We assess whether adding mammographic density (MD) information improves risk stratification on that cohort. Methods We used questionnaire data, baseline MD readings (using AutoDensity) and linked screening and cancer registry records from 40,158 BreastScreen Australia participants aged 50–69 years (via the lifepool cohort). We investigated incident invasive breast cancer rates by quintiles of Gail model scores, MD, and combinations of Gail and MD. Results Gail scores and MD values were weakly correlated (r≤0.02). Gail and MD were each strong predictors of incident breast cancer, but stronger predictors when used in combination. For example, the odds ratio for incident invasive breast cancer was 3.6 (95%CI 2.5-6.3) for the 17% of women in the upper two quintiles of both Gail and MD scores compared to the 17% of women in the lower two quintiles of both scores. In comparison, the odds ratio for breast cancer between same-size (each 17%) upper and lower groups for Gail score alone was 2.5 (95%CI 1.8-3.4), and for MD 1.9 (95%CI 1.2-2.9). Conclusions Combining Gail and MD categories improves risk stratification on BreastScreen Australia participants, compared to using Gail or MD alone. Key messages While questionnaire data and MD measures are each strong predictors of future invasive breast cancer among BreastScreen Australia participants, risk prediction is stronger when questionnaire and MD measures are combined.

A novel biosignature identifies DCIS patients with a poor biologic subtype with an unacceptably high rate of local recurrence after breast conserving surgery and radiotherapy.

513 Background: There is an unmet need to identify women diagnosed with DCIS who have a low recurrence risk and could omit radiotherapy (RT) after breast conserving surgery (BCS), or an elevated recurrence risk after treatment with BCS plus RT. DCISionRT and its response subtype (Rst) biosignature were evaluated in a contemporary cohort treated with BCS with or without RT to identify these risk groups. Methods: Pathology, clinical data, and FFPE tissue samples were evaluable for 485 women diagnosed with DCIS at centers in Sweden (1996-2004), the USA (1999-2008), and Australia (2006-2011). Patients were treated with BCS (negative margins) with or without whole breast RT. Ipsilateral breast tumor recurrence (IBTR) included DCIS or invasive breast cancer (IBC) that was local, regional, or metastatic. The patients were classified into Low and Elevated risk groups to assess IBTR and IBC rates. Patients in the Elevated risk group were categorized by two subtypes: a good response subtype (good Rst) or a poor response subtype (poor Rst) after BCS plus RT. Biosignatures were calculated using biomarkers (p16/INK4A, Ki-67, COX-2, PgR, HER2, FOXA1, SIAH2) assayed using IHC on FFPE tissue. Hazard ratios and 10-year risks were calculated using Cox proportional hazards (CPH) and Kaplan-Meier analyses. Results: In the DCISionRT Elevated risk group, RT was associated with significantly reduced recurrence rates, but only for those patients with a good Rst (Table, IBTR HR=0.18, p&lt;0.001, IBC HR=0.15, p=0.003, n=241). For Elevated risk group patients with a poor Rst, no benefit to RT was noted (Table). Additionally, irrespective of RT, patients with a poor Rst had 10-year IBTR/IBC rates of 25%/16%, which were much higher than good Rst rates of 6.6%/4.5% (IBE HR=3.6, p=0.02, IBC HR=4.4, p=0.04, n=190). For patients in the Low risk group, there was no significant difference in 10-year IBTR/IBC rates with and without RT (Table, IBTR p=0.4, IBC p=0.9, n=177). The distribution of clinicopathologic risk factors (age &lt;50 years, grade 3, size &gt;2.5 cm) did not identify poor vs. good response subtypes, and multivariable analysis (n=485) indicated these traditional clinicopathologic factors and endocrine therapy were not significantly associated with IBTR (p≥0.22) or IBC (p≥0.34). Conclusions: Biosignatures identified a Low risk patient group with low 10-year recurrence rates with or without RT who may be candidates for omitting adjuvant RT. Biosignatures also identified an Elevated risk group receiving BCS plus RT with a poor response subtype that had unacceptably high recurrence rates, warranting potential intensified or alternate therapy.[Table: see text]

Breast Cancer Incidence Reduction in Women Treated with Subcutaneous Testosterone: Testosterone Therapy and Breast Cancer Incidence Study.

Testosterone (T) therapy has been shown to be breast protective in both pre- and post-menopausal patients. Additionally, estradiol (E) does not cause breast cancer (BC) in the majority of the world's literatures. This study aimed to investigate the incidence of invasive BC (IBC) in pre- and postmenopausal women treated with T therapy and T in combination with E (T/E). Since January 2010, a total of 2,377 pre- and post-menopausal women were treated with T or T/E implants. IBC rates were reported based on newly diagnosed IBC cases in the total study. Total cases divided by the total sample size and years in study was expressed as an incidence per 100,000 person-years (P-Ys). The BC incidence was compared with age-specific Surveillance Epidemiology and End Results (SEER) incidence rates. As of October 2020, 14 cases diagnosed with IBC have been found in 9,746 P-Y of follow up for an incidence of 144 cases per 100,000 P-Y, substantially less than the age-specific SEER incidence rates (223/100,000), placebo arm of Women's Health Initiative Study (330/100,000), and never users of hormone therapy from the Million Women Study (312/100,000). T and/or T/E pellet implants significantly reduced the incidence of BC in pre- and post-menopausal women. The addition of E did not increase the incidence over using T alone. This is the second multi-year long-term study demonstrating the benefits of T therapy in reducing the incidence of IBC.

Breast cancer risk after age 60 amongBRCA1 andBRCA2 mutation carriers.

It is not known whether the risk of breast cancer among BRCA1 and BRCA2 mutation carriers after age 60 is high enough to justify intensive screening or prophylactic surgery. Thus, we conducted a prospective analysis of breast cancer risk in BRCA1 and BRCA2 mutation carriers from age 60 until age 80. Subjects had no history of cancer and both breasts intact at age 60 (n = 699). Women were followed until a breast cancer diagnosis, prophylactic bilateral mastectomy or death. We calculated the annual cancer rate and cumulative incidence of breast cancer (invasive and in situ) from age 60 to age 80. We assessed the associations between hormone replacement therapy, family history of breast cancer and bilateral oophorectomy and breast cancer risk. Over a mean follow-up of 7.9years, 61 invasive and 20 in situ breast cancers were diagnosed in the cohort. The mean annual rate of invasive breast cancer was 1.8% for BRCA1 mutation carriers and 1.7% for BRCA2 mutation carriers. The cumulative risk of invasive breast cancer from age 60 to 80 was 20.1% for women with a BRCA1 mutation and was 17.3% for women with a BRCA2 mutation. Hormone replacement therapy, family history and oophorectomy were not associated with breast cancer risk. Findings from this large prospective study indicate that the risk of developing breast cancer remains high after age 60 in both BRCA1 and BRCA2 mutation carriers. These findings warrant further evaluation of the role of breast cancer screening in older mutation carriers.

Abstract D020: Addressing the needs of Cedars-Sinai Cancer’s catchment area: Cancer screening compliance among the Korean community in Los Angeles

Abstract Background: Breast cancer screening rates among Korean American women lag behind other populations in the US; additionally, this population has the lowest mammography adherence rates of all the Asian subgroups. The rates of invasive breast cancer among Korean women in Los Angeles County (LAC) have also increased dramatically, which leads to poor outcomes. Early detection of breast cancer provides a greater range of treatment options and often better survival rates. Given this, we want to understand the unique barriers that Korean women in LAC face in order to adequately serve our catchment area. Methods: To understand the context of cancer screening compliance among Koreans in LAC, the Research Center for Health Equity (RCHE) at Cedars-Sinai Medical Center conducted a culturally adapted survey within its catchment area. We developed a Cancer and Healthcare in Los Angeles Survey (CHILAS) with feedback from Korean community leaders. The survey targeting females has 31 questions and covers screening behavior, medical history, and health care access. The survey was adapted with feedback from Korean community leaders and printed in the Korean language. A free cancer education workshop was offered post survey. For the purposes of the current analyses, we focused on participants were Korean women &amp;gt;= 18 yrs who reside in LAC. Surveys were administered at seven different faith-based venues, such as churches and Buddhist temples, during a three-month period. Results: 126 female participants were age eligible (age 45 and above) to answer the mammography screening cancer question and 52 (41.3%) of them had their screening up to date. 113 participants answered both the question about mammography screening and knowing someone with cancer. Of those who ‘knew someone with cancer’ (N=75), 46% had their screening up to date (N=35). Of those who ‘did not know someone with cancer’ (N=38), 34% had their screening up to date (N=13), the difference was not significant (p-value =0.21). Two of the top reasons for not getting screened were 1) not feeling sick and 2) no health insurance. Moreover, speaking the same language as the primary provider, financial status, length of waiting for an appointment, and transportation were not associated with breast cancer screening. Although mammography rates were low, colonoscopy rates among age eligible participants in the survey were very high (94.5%), leading us to believe there are unique factors to low mammography screening in Korean women. Future direction: To our knowledge, there are no existing awareness programs to increase mammography screening for this population. We know that faith-based organizations can increase screening behaviors among parishioners and can be an effective avenue for improving health outcomes. Through the engagement with elders, RCHE has formed an extensive network of partnerships with faith-based organizations we will identify the unique barriers to mammography compliance in Korean Americans. Citation Format: Dong Hee Kim, Yu-Chen Lin, Christie Y. Jeon, Laurel Finster, A. Joan Levine, Zul Surani, Robert W. Haile. Addressing the needs of Cedars-Sinai Cancer’s catchment area: Cancer screening compliance among the Korean community in Los Angeles [abstract]. In: Proceedings of the Twelfth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2019 Sep 20-23; San Francisco, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(6 Suppl_2):Abstract nr D020.

Hormone-replacement therapy may be associated with increased incidence of luminal breast cancer: Results from a large-scale health maintenance organization (HMO) analysis.

e13599 Background: Trends in breast cancer (BC) incidence may be impacted by potentially competing variables (e.g., mammography rates, hormone-replacement therapy [HRT] use). Methods: This observational retrospective study examined trends/associations between BC incidence, mammography rates, and HRT use among female members of the Maccabi Healthcare Services (the second largest HMO in Israel).BC subtypes were determined based on therapies received by patients diagnosed after 2006 (following trastuzumab approval in the adjuvant setting). Results: Between 2002 and 2014, 14,092 BC cases (88% invasive, 12% in-situ) were identified. The age-adjusted incidence rate of invasive BC peaked in 2005, consistent with increased mammography screening that year, and decreased thereafter. HRT use among all female members aged≥45 years decreased from 13.2% in 2002 to 4.6% in 2014, consistent with the global trend after the Women's Health Initiative publication. Analysis by BC subtype involved 6,218 invasive BC patients diagnosed between 2007 and 2014 (luminal A, 47.5%; luminal B1 without human epidermal growth factor receptor 2 [HER2] over-expression, 25.7%; luminal B2 with HER2 over-expression, 7.7%; estrogen receptor [ER]-negative/HER2+, 4.9%; triple negative, 8.3%; unknown, 6.0%). Overall, 75-86% of patients across all subtypes did not have any HRT exposure vs 14-25% who were current users (within 1 year before the BC diagnosis), recent users (within 2-5 years), or past users ( &gt; 5 years). Current and recent use of HRT was statistically significantly higher in luminal BC vs ER-negative tumors: rates in luminal A/B1/B2, 15.3%/12.1%/11.1% vs ER-negative HER2+/triple-negative/unknown, 8.9%/9.7%/7.7% ( P&lt; 0.001). In BC patients (≥45 years) with HRT exposure, the preparations used were estrogen plus progesterone (62%), estrogen alone (24%), and tibolone (14%). In non-BC cases (≥45 years), the respective values were similar: 61%, 26%, and 13%. Conclusions: HRT current/recent exposure may contribute to increased incidence of luminal BC tumors.

Accuracy and Effectiveness of Mammography versus Mammography and Tomosynthesis for Population-Based Breast Cancer Screening: A Systematic Review and Meta-Analysis

We proposed to compare the accuracy and effectiveness of digital breast tomosynthesis (DBT), plus digital or synthetic mammography, with digital mammography alone in women attending population-based breast cancer screenings. We performed a systematic review and included controlled studies comparing DBT with digital mammography for breast cancer screening. Search strategies were applied to the MEDLINE, Embase, LILACS, and CENTRAL databases. With moderate quality of evidence, in 1,000 screens, DBT plus digital mammography increased the overall and invasive breast cancer rates by 3 and 2 (RR 1.36, 95% CI 1.18 to 1.58 and RR 1.51, 95% CI 1.27 to 1.79, respectively). DBT plus synthetic mammography increased both overall and invasive breast cancer rates by 2 (RR 1.38, 95% CI 1.24 to 1.54 and RR 1.37, 95% CI 1.22 to 1.55, respectively). DBT did not improve recall, false positive and false negative rates. However due to heterogeneity the quality of evidence was low. For women attending population-based breast cancer screenings, DBT increases rates of overall and invasive breast cancer. There is no evidence with high or moderate quality showing that DBT compared with digital mammography decreases recall rates, as well as false positive and false negative rates.

Abstract A28: Current and future incidence rates of invasive breast cancer between Black and White women

Abstract Background: Though incidence rates for invasive breast cancer overall have been historically lower for Black than White women, recent reports show that rates have converged between the two groups. We used the age-period-cohort framework to verify the current trends and to forecast future implications. Methods: Data from Surveillance, Epidemiology, and End-Results (SEER) Program 13 registries and the age-period-cohort forecasting model were used to observe current incidence rates (1992 to 2014) and to predict future trends (2015 to 2030) of invasive breast cancer by ER status among non-Hispanic White, Hispanic, and Black women, ages 30 to 84 years. Trends in the age-standardized incidence rate (ASR) were quantitated with the estimated annual percentage change (EAPC) in the ASR. Results: Observed invasive breast cancer incidence rates from 1992 through 2014 show convergence between White and Black women but not between non-Hispanic White and Black women. Observed incidence rates for ER-positive breast cancer are rising for all races, but rising faster among Black women with an EAPC = 0.77 [0.26, 1.29] %/year. In contrast, observed incidence rates for ER-negative breast cancer are decreasing for all races, but decreasing slower among Black women with an EAPC = -2.00 [-2.55, -1.43] %/year. Forecasting for ER-positive and ER-negative breast cancers suggests a continuation of the observed trends without future convergence in overall breast cancer rates. Conclusions: Incidence rates between Black and White women did not converge when non-Hispanic White women were separated from Hispanic White women. Whenever possible, future comparative breast cancer analyses should always attempt to analyze discrete populations separately, given the complexities of differential risk factor exposures by race and/or ethnicity. A better understanding of breast cancer in general and by race may be accomplished by accurately describing the similarities and disparities among different ethnic groups. Citation Format: Brittny C. Davis Lynn, Philip S. Rosenberg, William F. Anderson. Current and future incidence rates of invasive breast cancer between Black and White women [abstract]. In: Proceedings of the Tenth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2017 Sep 25-28; Atlanta, GA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2018;27(7 Suppl):Abstract nr A28.

Breast Density and Risk of Invasive Breast Cancer among Older Women Undergoing Mammography: The Breast Cancer Surveillance Consortium Cohort Study

Abstract This study examined whether breast density is associated with risk of breast cancer in women age ≥65 years undergoing screening mammography in community practice. Methods: We used prospective cohort data between 1996 and 2012 from the Breast Cancer Surveillance Consortium (BCSC). We calculated separate cumulative incidence models for breast cancer incidence according to Breast Imaging Reporting and Data System (BI-RADS) breast density for women ages 65–74 and ages ≥75. Multivariable Cox proportional hazards regression models were fitted to determine the risk of invasive breast cancer adjusted for BCSC registry, race/ethnicity, BMI, hormone therapy use and benign breast disease. Results: Among the 403,268 women included in the study, approximately 40% were ages ≥75. The annual incidence rate of invasive breast cancer increased with increasing breast density among women ages 65–74 [BI- RADS fatty breasts: 2.2% (95% CI, 2.1%–2.4%) vs. heterogeneously or extremely dense breasts: 4.7% (95% CI, 4.6%–4.9%)] and women ages 75+ [BI-RADS fatty breasts: 2.3% (95% CI, 2.1%–2.5%) vs. heterogeneously or extremely dense: 4.3% (95% CI, 4.1%–4.5%)]. Women with BI-RADS fatty breasts had a decreased risk of breast cancer among women ages 65–74 [HR: 0.66 (95% CI: 0.58%–0.78%) and women ages ≥75 [HR: 0.73 (95% CI: 0.62%–0.87%). Women with BI-RADS heterogeneously or extremely dense breasts were found to have increased risk of breast cancer among women ages 65–74 [HR: 1.39 (95% CI: 1.28%–1.51%)] and women ages ≥75 [HR: 1.23 (95% CI: 1.10%–1.37%)]. Conclusions: Older women with higher BI-RADS density had a significantly increased risk of breast cancer. These findings add further evidence that breast density continues to be associated with an increased risk of breast cancer, even among women age ≥75 years.

Abstract P4-15-04: A longitudinal cohort study to identify risk factors for the development of invasive cancer in unresected DCIS

Abstract Background: The variable natural history of ductal carcinoma in situ (DCIS) remains poorly understood. Randomized trials of active surveillance versus guideline concordant care are currently underway: the Comparison of Operative to Monitoring and Endocrine Therapy (COMET) trial in the US, LOw Risk dcIS (LORIS) trial in the UK and Low Risk Dcis (LORD) in Europe. Given this context, we examined the outcomes of a contemporary group of women with DCIS who did not undergo initial surgical resection. Methods: A longitudinal cohort of women diagnosed with DCIS on needle biopsy who did not undergo initial surgical excision for ≥1 year were identified through the Cancer Registry with case note and death certificate review for subsequent outcomes. Results: Eighty-nine eligible women with DCIS alone diagnosed on needle biopsy (most with 14-gauge core needle biopsy) between 1998 and 2010 were identified. The mean age at diagnosis was 72 years (range 44-94 years) with mean follow-up (diagnosis to death, invasive disease or last review) of 62 months (range 12-180 months). Twenty-nine women (33%) developed histologically proven invasive breast cancer, 28 at the site of the initial DCIS biopsy, after a mean interval of 54 months (range 12-144 months): 14/29 (48%) women originally had high grade DCIS, 10/31 (32%) intermediate grade and 3/17 (18%) low grade DCIS (initial grade not known in 12). Time to detect a diagnosis of invasive breast cancer was associated with initial grade of DCIS (p=0.0016, log-rank test): after mean intervals of 41 months (high grade), 69 months (intermediate grade) and 78 months (low grade) respectively. Younger age was associated with development of invasive disease (p&amp;lt;0.003, Mann-Whitney U-Test). High grade (grade 3) invasive breast cancer exclusively occurred in women with a prior diagnosis of high grade DCIS. Invasion was more frequent in lesions with calcification as the predominant feature than those without (23/50 v. 5/25; p&amp;lt;0.05, Fisher exact test). Forty-four women were prescribed endocrine therapy, use of which was associated with a lower rate of invasive breast cancer (p&amp;lt;0.05). Ultimately 18 women underwent surgery, 17 for invasive cancer. The mean interval from DCIS diagnosis to death was 76 months for those who developed invasive cancer; 48/89 women died, 12 had a certified cause of death as breast cancer. Conclusion: High grade DCIS, mammographic microcalcification and lack of endocrine therapy were associated with progression to invasion. The findings suggest surgical excision of high grade DCIS should continue but provides support that women with DCIS features which include low grade should be considered for the COMET, LORIS or LORD active surveillance trials. Citation Format: Maxwell AJ, Clements K, Hilton B, Dodwell DJ, Evans A, Olive K, Pinder SE, Thomas J, Matthew WG, Thompson AM. A longitudinal cohort study to identify risk factors for the development of invasive cancer in unresected DCIS [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P4-15-04.

Risk factors for the development of invasive cancer in unresected ductal carcinoma in situ

BackgroundThe natural history of ductal carcinoma in situ (DCIS) remains uncertain. The risk factors for the development of invasive cancer in unresected DCIS are unclear. MethodsWomen diagnosed with DCIS on needle biopsy after 1997 who did not undergo surgical resection for ≥1 year after diagnosis were identified by breast centres and the cancer registry and outcomes were reviewed. ResultsEighty-nine women with DCIS diagnosed 1998–2010 were identified. The median age at diagnosis was 75 (range 44–94) years with median follow-up (diagnosis to death, invasive disease or last review) of 59 (12–180) months. Twenty-nine women (33%) developed invasive breast cancer after a median interval of 45 (12–144) months. 14/29 (48%) with high grade, 10/31 (32%) with intermediate grade and 3/17 (18%) with low grade DCIS developed invasive cancer after median intervals of 38, 60 and 51 months. The cumulative incidence of invasion was significantly higher in high grade DCIS than other grades (p = .0016, log-rank test). Invasion was more frequent in lesions with calcification as the predominant feature (23/50 v. 5/25; p = .042) and in younger women (p = .0002). Endocrine therapy was associated with a lower rate of invasive breast cancer (p = .048). ConclusionsHigh cytonuclear grade, mammographic microcalcification, young age and lack of endocrine therapy were risk factors for DCIS progression to invasive cancer. Surgical excision of high grade DCIS remains the treatment of choice. Given the uncertain long-term natural history of non-high grade DCIS, the option of active surveillance of women with this condition should be offered within a clinical trial.

Obligate Overdiagnosis Due to Mammographic Screening: A Direct Estimate for U.S. Women.

Purpose To determine obligate overdiagnosis rates, defined as the percentage of women diagnosed with screen-detected breast cancer who die of causes other than breast cancer prior to clinical presentation of that cancer, for ductal carcinoma in situ (DCIS), invasive breast cancer, and all breast cancers. Materials and Methods Age-specific all-cause mortality rates from the Human Mortality Database, age-specific breast cancer incidence and mortality rates from Surveillance, Epidemiology, and End Results data, and estimates of mean lead times and lead time distributions from breast cancer screening trials are used to estimate obligate (or type 1) overdiagnosis rates for DCIS, invasive breast cancer, and all breast cancers (DCIS plus invasive) for U.S. women undergoing screening mammography. Mortality rates by age are used to estimate the number of women who die of causes other than breast cancer during the lead time afforded by screening mammography. Resulting age-dependent overdiagnosis rates, along with screen-detected breast cancer incidence by age, are used to estimate type 1 overdiagnosis rates for the U.S. screening population. Results Obligate overdiagnosis rates depend strongly on the age at which a woman is screened, ranging from less than 1% at age 40 years to 30%, 21%, and 22.5% at age 80 years for DCIS, invasive breast cancer, and all breast cancers, respectively. Type 1 overdiagnosis rates among screened women in the United States are estimated to be 9% for DCIS and approximately 7% for both invasive breast cancer and all breast cancers. Screening of women ages 40-49 years (or premenopausal women, as determined from patient history, starting at age 40 years) adds little to obligate overdiagnosis rates (0.15% for DCIS and less than 0.1% for invasive breast cancer and all breast cancers). Conclusion Type 1 overdiagnosis rates increase rapidly with age at screening. Obligate overdiagnosis occurs in 9% of DCIS and approximately 7% of both invasive breast cancer and all breast cancers in the U.S. mammographic screening population, with screening of women ages 40-49 years (or premenopausal women starting at age 40 years) making a negligible contribution of 0.15% to obligate overdiagnosis of DCIS and a contribution of less than 0.1% to the obligate overdiagnosis rates of invasive breast cancer and all breast cancers. © RSNA, 2017 Online supplemental material is available for this article.