Rates Of Triple-negative Breast Cancer Research Articles

Abstract C072: Structural racism and race- and subtype-specific breast cancer incidence in California, 2006-2015

Abstract Background: Breast cancer is the most commonly diagnosed noncutaneous cancer and the second leading cause of death from cancer among women in the United States. Breast cancer is a heterogeneous disease and subtypes defined by hormone-receptor (HR) and HER2Neu status have distinct etiologic and prognostic profiles. African American women are more likely than White women to be diagnosed with HR-/HER2-, or triple-negative, breast cancer (TNBC), which is more aggressive and has a higher fatality rate than HR+ subtypes, including Luminal A. Determinants of racial disparities in breast cancer subtype are poorly understood. African Americans have historically been, and continue to be, subjected to institutionalized discrimination. Such discrimination, including housing discrimination, may contribute to breast cancer disparities, particularly, higher rates of TNBC among African American women. The aim of this study was to characterize the association between racial bias in mortgage lending and race- and subtype-specific breast cancer incidence rates in California. Methods: We merged data from the California Cancer Registry on all women aged 20+ diagnosed with primary breast cancer between 2006-2015 with census tract characteristics where cases reside at time of diagnosis, including a new racial bias index, generated using data from the Home Mortgage Disclosure Act, 2007-2013. Racial bias was operationalized as the odds of a mortgage application denial for a Black applicant as compared to a White applicant, adjusting for individual sex, and the ratio of the loan amount to the applicant's gross annual income. We classified census tracts with an average Black-White mortgage denial OR>2.5 as “high anti-Black bias.” Using Poisson regression with generalized estimating equations, we estimated the association between anti-Black bias and race-, age-, and subtype-specific breast cancer case counts, with population size as offset, and adjusting for census tract average age, socioeconomic status, racial composition, and residential stability. Results: We identified n=104,716 cases of Luminal A breast cancer and n=14,238 cases of TNBC over the study period. Among White—but not African American—women, living in a census tract with high anti-Black bias was positively associated with incidence of Luminal A breast cancer (IRR=1.05, 95% CI=1.03, 1.07). This association was only slightly attenuated after adjusting for tract-level demographics (IRR=1.02, 95% CI=1.01, 1.04). No association was found between anti-Black bias and TNBC among either racial group (White IRR=1.00, 95% CI=0.96, 1.03; Black IRR=1.00, 95% CI=0.93, 1.01). Conclusion: Among White women, living in communities with high levels of anti-Black housing discrimination may be associated with increased risk of Luminal A breast cancer. Future research into the psychosocial and/or material mechanisms underpinning this association is warranted. Citation Format: Elizabeth Michaels, Kirsten Beyer, Alison Canchola, Yuhong Zhou, Scarlett Gomez. Structural racism and race- and subtype-specific breast cancer incidence in California, 2006-2015 [abstract]. In: Proceedings of the Eleventh AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2018 Nov 2-5; New Orleans, LA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(6 Suppl):Abstract nr C072.

Comparing Clinicopathologic Features and Surgical Treatment of Premenopausal Breast Cancer across Italy and China: Report from a Medical Exchange Program

Background: This study investigated the differences in clinicopathologic features and surgical treatment between an Italian and a Chinese cohort of premenopausal women with breast cancer, and highlighted the potential advantages of international medical exchange projects. Methods: Premenopausal women who underwent surgical treatment between 2012 and 2016 at one Italian and one Chinese institution participating in a medical exchange program were compared. Factors associated with the probability to receive mastectomy were determined via logistic analysis. Changes in surgical management at the Chinese institution in the period 2018–2019, after the exchange program, were also evaluated. Results: A total of 505 patients, 318 from Italy and 187 from China, were evaluated. The Chinese patients had more frequently advanced-stage tumours, large tumour size (30.9 vs. 18.1 mm, p < 0.01), invasive carcinoma (92.5 vs. 83.3%, p < 0.01), positive axillary lymph nodes (54.5 vs. 27.4%, p < 0.01), Her-2 positivity (36.4 vs. 22.0%, p < 0.01), and high proliferative index (55.1 vs. 30.2%, p < 0.01). Positive oestrogen receptor status and rates of triple-negative breast cancer did not differ (77.0 vs. 69.5%, p = 0.09 and 14.2 vs. 16%, p = 0.56, respectively). Mastectomy rates were higher among Chinese women (85 vs. 41%, p < 0.001), whereas use of sentinel node biopsy was more frequent among Italian women (77 vs. 33%, p < 0.001). Chinese women had more than 4-fold higher risk of receiving mastectomy. In the last 2 years, the rates of breast-conserving surgery and sentinel node biopsy at the Chinese institution increased from 15 to 23%, and from 33 to 42%, respectively. Conclusions: Tumour features and surgical strategies for premenopausal breast cancer may differ significantly between Italy and China. Since the international exchange program, patients from the Chinese institution have been offered more frequently less invasive surgery. International exchange programs can help in designing epidemiological studies which may be useful for strategies to improve breast cancer management and control.

Disparities in breast cancer subtypes among women in the lower Mississippi Delta Region states.

To describe and elucidate rates in breast cancer incidence by subtype in the federally designated Mississippi Delta Region, an impoverished region across eight Southern/Midwest states with a high proportion of Black residents and notable breast cancer mortality disparities. Cancer registry data from seven LMDR states (Missouri was not included because of permission issues) were used to explore breast cancer incidence differences by subtype between the LMDR's Delta and non-Delta Regions and between White and Blackwomen within the Delta Region (2012-2014). Overall and subtype-specific age-adjusted incidence rates and rate ratios were calculated. Multilevel negative binomial regression models were used to evaluate how individual-level and area-level factors, like race/ethnicity and poverty level, respectively, affect rates of breast cancers by subtype. Women in the Delta Region had higher rates of triple-negative breast cancer, the most aggressive subtype, than women in the non-Delta (17.0 vs. 14.4 per 100,000), but the elevated rate was attenuated to non-statistical significance in multivariable analysis. Urban Delta women also had higher rates of triple-negative breast cancer than non-Delta urban women, which remained in multivariable analysis. In the Delta Region, Black women had higher overall breast cancer rates than their White counterparts, which remained in multivariable analysis. Higher rates of triple-negative breast cancer in the Delta Region may help explain the Region's mortality disparity. Further, an important area of future research is to determine what unaccounted for individual-level or social area-level factors contribute to the elevated breast cancer incidence rate among Black women in the Delta Region.

Abstract P5-13-08: Association of tumor infiltrating lymphocytes and chemotherapy regimen in response to preoperative chemotherapy in underserved patients

Abstract Introduction Preoperative chemotherapy can demonstrate an individual's response to the chemotherapeutic regimen by comparing the amount of cancer at presentation to the amount remaining after treatment. Multiple previous studies have demonstrated that the amount of residual cancer, or final pathologic stage, is a better indicator of prognosis than the initial stage at presentation. Tumor infiltrating lymphocytes have been recognized in breast cancer, and when found concentrated in breast cancer specimens, have been associated with a good prognosis. Breast cancer is not only a heterogeneous disease, but also displays varied presentation and behavior in patients of different race/ethnicities. This study was performed to evaluate factors which predict response to chemotherapy. The effectiveness of different chemotherapeutic regimens, the effect of breast cancer subtype, and tumor infiltrating lymphocytes (TILs) were evaluated in our racial/ethnic minority population. Methods All patients at the safety net institution in Phoenix, AZ who underwent preoperative chemotherapy from 2002 to 2017 and had tissue available for evaluation were included in the study. Response to chemotherapy regimen was recorded. Pathologic complete response (pCR) was defined as no invasive cancer in the breast and lymph nodes in the final pathologic specimen. Breast cancer subtypes were divided based on IHC and FISH testing. Luminal subtypes were classified based on Ki67 (&amp;gt;15%) and/or PR (&amp;lt;20%) for Luminal B. Her2 subtype was defined as Her2 IHC 3+ or Her2 FISH amplified. Triple negative breast cancer (TNBC) was defined as ER and PR (&amp;lt;5%) and Her2 negative. TILs concentration was determined from fixed formalin paraffin embedded (FFPE) core needle biopsy specimens. Results A total of 259 patients were included in the study. The mean age was 45 years. 80% of the population were racial/ethnic minorities. The vast majority (94%) were underinsured or uninsured, with 75% uninsured. The mean clinical tumor size at presentation was 6cm. 52% presented at clinical stage 2 while 48% presented at clinical stage 3. The overall pCR rate was 32%. pCR rate was impacted by breast cancer subtype with TNBC 52% and Her2 38% showing a better response to chemotherapy, while Luminal B was 16% and Luminal A 2% (p &amp;lt; 0.05). In TNBC, chemotherapy regimens with anthracycline and docetaxel may have improved efficacy with pCR of 56% (p = 0.05). In the subgroup available for TIL evaluation, breast cancer subtype appeared to show similar importance with pathologic complete response rates of TNBC 50%, Her2 44%, Luminal B 12%, and Luminal A 0%. TIL appeared to affect the likelihood of pCR. When TIL were less than 5% the pCR rate was 16% compared to when there were TIL of at least 5% or more the pCR rate was 41% (p &amp;lt; 0.05). Conclusions In our racial/ethnic minority population, breast cancer subtype and chemotherapy regimen did affect likelihood of pathologic complete response. Tumor infiltrating lymphocyte concentration as low as 5% may indicate a higher likelihood of pathologic complete response and could be used as an additional factor in the evaluation of patients for preoperative therapy. Citation Format: Komenaka IK, Cocco D, Huliyar R, Hsu C-H, Martinez ME, Gago M, Nodora J, Mehta D, Caruso DM. Association of tumor infiltrating lymphocytes and chemotherapy regimen in response to preoperative chemotherapy in underserved patients [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P5-13-08.

The Effect of Insurance and Race on Breast Cancer Tumor Biology and Short-Term Outcomes

To determine whether low-income status as demonstrated by insurance type has any association with aggressive tumor biology and breast cancer outcomes. Retrospective review of 535 women with new diagnosis of breast cancer from January 2009 to March 2013 was performed. There was no significant association between race and stage at diagnosis. Women with Medicaid/Charity coverage were diagnosed at more advanced stages, more likely to have triple-negative breast cancer (TNBC), and had longer time to treatment. Rate of TNBC was higher in black women and younger patients. There was no significant difference in breast cancer recurrence or survival by race, insurance type, age, or tumor biology. In multivariable analysis, only black race (P = 0.003) and Medicaid/Charity Insurance (P = 0.0008) were the most significant predictors of TNBC. Presentation of aggressive tumor biology and advanced stage is strongly associated with socioeconomic factors as reflected by Medicaid funding and lack of insurance.

Prediction of treatment responses to neoadjuvant chemotherapy in triple-negative breast cancer by analysis of immune checkpoint protein expression

Background“Avoiding immune destruction” has recently been established as one of the hallmarks of cancer. The programmed cell death (PD)-1/programmed cell death-ligand (PD-L) 1 pathway is an important immunosuppression mechanism that allows cancer cells to escape host immunity. The present study investigated how the expressions of these immune checkpoint proteins affected responses to neo-adjuvant chemotherapy (NAC) in breast cancer.MethodsA total of 177 patients with resectable early-stage breast cancer were treated with NAC. Estrogen receptor, progesteron receptor, human epidermal growth factor receptor 2, Ki67, PD-L1, PDL-2 and PD-1 status were assessed by immunohistochemistry.ResultsThere were 37 (20.9%) patients with high PD-1 expression, 42 (23.7%) patients had high PD-L1 expression, and 52 (29.4%) patients had high PD-L2 expression. The patients with high PD-1 and PD-L1 expressions had a significantly higher rate of triple-negative breast cancer (TNBC) (p = 0.041) (p < 0.001). In TNBC, patients with high PD-1 and PD-L1 expressions had significantly higher rates of non-pCR (p = 0.003) (p < 0.001). Univariate analysis showed that PD-1 and PD-L1 expressions also significantly shortened disease free survival in TNBC (p = 0.048, HR = 3.318) (p = 0.007, HR = 8.375). However, multivariate analysis found that only PD-L1 expression was an independent prognostic factor (p = 0.041, HR = 9.479).ConclusionsPD-1 and PD-L1 expressions may be useful as biomarkers to predict treatment responses to NAC in breast cancer. Above all, PD-L1 expression may also be useful as biomarkers for more effective chemotherapy in TNBC.

Breastfeeding and Breast Cancer Risk Reduction: Implications for Black Mothers

Breast cancer is the most commonly diagnosed cancer and a leading cause of death from cancer among U.S. women. Studies have suggested that breastfeeding reduces breast cancer risk among parous women, and there is mounting evidence that this association may differ by subtype such that breastfeeding may be more protective of some invasive breast cancer types. The purpose of this review is to discuss breast cancer disparities in the context of breastfeeding and the implications for black mothers. Black women in the U.S. have lower rates of breastfeeding and nearly twice the rates of triple-negative breast cancer (an aggressive subtype) compared with white women. In addition to individual challenges to breastfeeding, black women may also differentially face contextual barriers such as a lack of social and cultural acceptance in their communities, inadequate support from the healthcare community, and unsupportive work environments. More work is needed to improve the social factors and policies that influence breastfeeding rates at a population level. Such efforts should give special consideration to the needs of black mothers to adequately address disparities in breastfeeding among this group and possibly help reduce breast cancer risk. Interventions such as peer counseling, hospital policy changes, breastfeeding-specific clinic appointments, group prenatal education, and enhanced breastfeeding programs have been shown to be effective in communities of color. A comprehensive approach that integrates interventions across multiple levels and settings may be most successful in helping mothers reach their breastfeeding goals and reducing disparities in breastfeeding and potentially breast cancer incidence.

TREATMENT OF TRIPLE-NEGATIVE BREAST CANCER

The rate of triple-negative breast cancer is 10–24 %, and in recent years it’s one of the most studied subtypes of breast cancer due to its clinical aggressiveness and a small number of molecular targets. The study objective is to evaluate effectiveness of different NAPCT regimens including their dependence on the presence of mutations in the ВRСА 1, 2, СHEK2 genes. Materials and methods . The study included 40 female patients with triple-negative breast cancer. The patients were monitored from 2012 to 2016; surgical treatment was performed at the P.A. Hertzen Moscow Oncology Research Institute – branch of the National Medical Research Radiological Center, Ministry of Health of Russia. Median patient age was 45.9 (31–69) years. All patients received neoadjuvant polychemotherapy (NAPCT) per different regimens. Then the patients underwent surgery of different volume (from radical mastectomies to resections), and in 25 % of cases reconstructive breast surgery was performed. In 5 patients with BRCA1, – 2 mutations, prophylactic subcutaneous mastectomy with immediate reconstruction with an implant was performed; 2 patients refused prophylactic mastectomy; in 1 patient with СНЕК2 mutation, metachronous multiple primary breast cancer was diagnosed, previously she didn»t undergo prophylactic mastectomy, and 6 years later cancer in the second breast was diagnosed. Results. The study included 11 patients under 40 (27.5 %), 4 (50 %) of them in the group with mutations in ВRCA1, -2, CHEK2. The study demonstrated high effectiveness of NAPCT regimens per the АС + Т scheme and weekly injections of doxorubicin 25 mg/m 2 , cisplatin 30 mg/m 2 , and paclitaxel 100 mg/m 2 . Grade IV treatment pathomorphosis for NAPCT per АС + Т scheme was achieved in 50.0 ± 7.9 % cases, for intensified regimen – in 62.5 ± 12.5 % cases. Median follow-up duration for this patient group was 22.1 months, and during this time disease progression was observed in 3 patients: in the 1st patient continued growth on the thoracic wall and brain metastases were diagnosed, in the 2nd patient – lung and supraclavicular lymph nodes metastases, in the 3rd patient – metastases in the cerebellum. In all of these patients, grade IV treatment pathomorphosis wasn»t achieved. Conclusions. The study demonstrated high effectiveness of NAPCT in patients with triple-negative breast cancer of different stages: objective response rate was 90.0 ± 4.7 %, grade IV treatment pathomorphosis was 50.0 ± 7.9 %. Grade IV treatment pathomorphosis for NAPCT per АС + Т scheme was achieved in 50.0 ± 7.9 % cases, for intensified regimen – in 62.5 ± 12.5 % cases. Rate of grade IV treatment pathomorphosis was higher in patients with hereditary form of the disease (62.5 ± 18.3 %) compared to the group with sporadic breast cancer (46.9 ± 8.8 %), р >0.05. In all patients, 2-year disease-free survival was 92.5 %, 2-year overall survival was 95 %.

Prevalence of Triple-Negative Breast Cancer in India: Systematic Review and Meta-Analysis.

PurposeThere is considerable variation in prevalence rates of triple-negative breast cancer (TNBC) reported by various studies from India. We performed a systematic review and literature-based meta-analysis of these studies.MethodsWe searched databases of Medline, Scopus, EMBASE, and Web of Science for studies that reported on the prevalence of TNBC in India that were published between January 1, 1999, and December 31, 2015. We extracted relevant information from each study by using a standardized form. We pooled study-specific estimates by using random-effects meta-analysis to provide summary estimates. We explored sources of heterogeneity by using subgroup analyses and metaregression.ResultsData were obtained from 17 studies that involved 7,237 patients with breast cancer. Overall combined prevalence of TNBC was 31% (95% CI, 27% to 35%). There was substantial heterogeneity across the studies (I2 of 91% [95% CI, 88% to 94%]; P < .001) that was not explained by available study level characteristics, including study location, definition of human epidermal growth factor receptor 2 or estrogen receptor, mean age of participants, proportion of patients with premenopausal cancer, grade 3 disease, or tumor size > 5 cm. Overall combined prevalence of hormone receptor–positive and human epidermal growth factor receptor 2–positive breast cancer was 48% (95% CI, 42% to 54%) and 27% (95% CI, 24% to 31%), respectively. There was no evidence of publication bias.ConclusionPrevalence of TNBC in India is considerably higher compared with that seen in Western populations. As many as as one in three women with breast cancer could have triple-negative disease. This finding has significant clinical relevance as it may contribute to poor outcomes in patients with breast cancer in India. Additional research is needed to understand the determinants of TNBC in India.

Abstract IA29: Race, ethnicity, and outcomes in breast cancer

Abstract The racial divide in breast cancer outcomes is well known. Breast cancer is the most common cause of cancer in women in the United States, and the second leading cause of cancer death.1 Black race is associated with a worse prognosis in operable breast cancer2 and in other hormone dependent cancers such as uterine and prostate cancer, but generally not other cancer types.3,4 Black women are more likely to present with advanced stage disease5, have triple negative breast cancer (TNBC), exhibit greater non-adherence and poorer tolerance to chemotherapy6 and endocrine therapy7, and have more comorbidities8 and experience more disparities in care.9-11 Black race has also been associated with worse outcome in male breast cancer.12 Although breast cancer incidence and mortality have declined by about 35% in the United States since 1990, mortality rates have declined less in black women, contributing to a widening of the racial gap which has contributed to about a 35% higher mortality rate for black women compared with others.13 However, a widening racial gap has also been observed for women in the U.S. Department of Defense healthcare system, suggesting that factors other than disparities in care may be playing a role. 14 With regard to ethnicity, Hispanic women also exhibit higher rates of TNBC, but otherwise experience similar outcomes as non-Hispanic women. There is emerging evidence that differences in outcomes may be due in part due to factors other than disparities in care. In this review, we explore some of the biological factors that may be contributing to the racial divide in breast cancer.

Abstract P1-09-04: New Orleans has the highest incidence rates of triple negative breast cancer

Abstract Background: We previously demonstrated increased incidence rates of triple negative breast cancer (TNBC) in Black women (BW) in New Orleans (NO) and Louisiana (LA) compared with SEER 17. We explored the hypothesis that BW in NO had a higher incidence of TNBC than in BW other metro areas in the SEER Program. Methods: We analyzed tumor characteristics of invasive female breast cancers diagnosed 2010-12 from SEER, focusing on racial disparities. We compared LA data with SEER 17 and metropolitan areas (Atlanta, Detroit, Los Angeles and San Francisco). Predictors of TNBC were identified in multivariate logistic regression. Results: Overall incidence rate of TNBC in BW was significantly higher in NO (32 per 100,000) than in the rest of LA (24 per 100,000) and the SEER metro areas combined (23 per100,000). Detroit had the 2nd highest rates (27.3 per 100,000) followed by Los Angeles, San Francisco and Atlanta (23.2, 23, 22.4 respectively). Compared with SEER 17, the rate ratio of TNBC was 38% higher for BW in NO (CI: 1.17-1.61) and 17% higher for BW in Detroit (CI: 1.06-1.29). Compared with other LA metro areas, the rate ratio of TNBC was 44% higher for BW in NO (CI: 1.10-1.91). Young age (&amp;lt;65) and black race predicted TNBC after adjusting for insurance status, tumor size, lymph node status, grade and derived AJCC stage. Conclusions: The incidence rates and rate ratios of TNBC in BW in NO and LA are not only significantly higher than in SEER 17 but also higher than any other SEER metro area. We will explore this dataset further by analyzing BMI, comorbidities and SES. This disparity in BW in NO has clinical implications and translational research potential as it enables us to broaden the understanding and treatment of this aggressive disease. Citation Format: Loch MM, Li X, Hsieh M-C, Chen VW, Wu X-C. New Orleans has the highest incidence rates of triple negative breast cancer. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P1-09-04.

Neural stem cell-mediated intratumoral delivery of gold nanorods improves photothermal therapy.

Plasmonic photothermal therapy utilizes biologically inert gold nanorods (AuNRs) as tumor-localized antennas that convert light into heat capable of eliminating cancerous tissue. This approach has lower morbidity than surgical resection and can potentially synergize with other treatment modalities including chemotherapy and immunotherapy. Despite these advantages, it is still challenging to obtain heating of the entire tumor mass while avoiding unnecessary collateral damage to surrounding healthy tissue. It is therefore critical to identify innovative methods to distribute an effective concentration of AuNRs throughout tumors without depositing them in surrounding healthy tissue. Here we demonstrate that AuNR-loaded, tumor-tropic neural stem cells (NSCs) can be used to improve the intratumoral distribution of AuNRs. A simple UV–vis technique for measuring AuNR loading within NSCs was established. It was then confirmed that NSC viability is unimpaired following AuNR loading and that NSCs retain AuNRs long enough to migrate throughout tumors. We then demonstrate that intratumoral injections of AuNR-loaded NSCs are more efficacious than free AuNR injections, as evidenced by reduced recurrence rates of triple-negative breast cancer (MDA-MB-231) xenografts following NIR exposure. Finally, we demonstrate that the distribution of AuNRs throughout the tumors is improved when transported by NSCs, likely resulting in the improved efficacy of AuNR-loaded NSCs as compared to free AuNRs. These findings highlight the advantage of combining cellular therapies and nanotechnology to generate more effective cancer treatments.

Re: Age-Specific Incidence of Breast Cancer Subtypes: Understanding the Black–White Crossover

Background Breast cancer incidence is higher among black women than white women before age 40 years, but higher among white women than black women after age 40 years (black–white crossover). We used newly available population-based data to examine whether the age-specific incidences of breast cancer subtypes vary by race and ethnicity. Methods We classified 91908 invasive breast cancers diagnosed in California between January 1, 2006, and December 31, 2009, by subtype based on tumor expression of estrogen receptor (ER) and progesterone receptor (PR)—together referred to as hormone receptor (HR)—and human epidermal growth factor receptor 2 (HER2). Breast cancer subtypes were classified as ER or PR positive and HER2 negative (HR+/HER2−), ER or PR positive and HER2 positive (HR+/HER2+), ER and PR negative and HER2 positive (HR−/HER2+), and ER, PR, and HER2 negative (triple-negative). We calculated and compared age-specific incidence rates, incidence rate ratios, and 95% confidence intervals by subtype and race (black, white, Hispanic, and Asian). All P values are two-sided. Results We did not observe an age-related black–white crossover in incidence for any molecular subtype of breast cancer. Compared with white women, black women had statistically significantly higher rates of triple-negative breast cancer at all ages but statistically significantly lower rates of HR+/HER2− breast cancers after age 35 years (all P < .05). The age-specific incidence of HR+/HER2+ and HR−/HER2+ subtypes did not vary markedly between white and black women. Conclusions The black–white crossover in breast cancer incidence occurs only when all breast cancer subtypes are combined and relates largely to higher rates of triple-negative breast cancers and lower rates of HR+/HER2− breast cancers in black vs white women.

Predictors of neoadjuvant chemotherapy for triple-negative breast cancer: a meta-analysis with 723 cases

Neoadjuvant chemotherapy (NAC) was increasingly used as a systemic therapy for triple-negative breast cancer (TNBC). The pathological complete response (PCR) rates of neoadjuvant chemotherapy in TNBC were higher than other types of breast cancer with fluctuate data. Predictors to identify which subgroup TNBC was more likely to achieve PCR in neoadjuvant chemotherapy would give us some hints on how to improve outcomes of TNBC patients. The meta-analysis was conducted to contrast the prognostic function of some clinicopathological parameters in the PCR rates of neoadjuvant chemotherapy for TNBC. Studies were selected from the PubMed database. The relevant parameters to PCR rates in TNBC group were recorded. Review Manager and MIX were used to estimate prognostic function of some biological markers and clinicopathological parameters in PCR rates of TNBC. The analysis included 6 studies with 723 patients, the aggregate PCR rate was 27.9% in TNBC group. The association of lymph nodes metastasis, Ki-67 expression, p53 expression and CK5/6 expression with PCR rate of TNBC was investigated in the analysis, and the odds ratios were 0.50, 9.87, 1.17 and 0.53 respectively. This meta-analysis demonstrated that Ki-67 expression and lymph nodes metastasis were predictors of PCR rate for TNBC in neoadjuvant chemotherapy, while p53 and CK5/6 expression could not be confirmed for the prognostic function.

Age-Specific Incidence of Breast Cancer Subtypes: Understanding the Black–White Crossover

Breast cancer incidence is higher among black women than white women before age 40 years, but higher among white women than black women after age 40 years (black-white crossover). We used newly available population-based data to examine whether the age-specific incidences of breast cancer subtypes vary by race and ethnicity. We classified 91908 invasive breast cancers diagnosed in California between January 1, 2006, and December 31, 2009, by subtype based on tumor expression of estrogen receptor (ER) and progesterone receptor (PR)-together referred to as hormone receptor (HR)-and human epidermal growth factor receptor 2 (HER2). Breast cancer subtypes were classified as ER or PR positive and HER2 negative (HR(+)/HER2(-)), ER or PR positive and HER2 positive (HR(+)/HER2(+)), ER and PR negative and HER2 positive (HR(-)/HER2(+)), and ER, PR, and HER2 negative (triple-negative). We calculated and compared age-specific incidence rates, incidence rate ratios, and 95% confidence intervals by subtype and race (black, white, Hispanic, and Asian). All P values are two-sided. We did not observe an age-related black-white crossover in incidence for any molecular subtype of breast cancer. Compared with white women, black women had statistically significantly higher rates of triple-negative breast cancer at all ages but statistically significantly lower rates of HR(+)/HER2(-) breast cancers after age 35 years (all P < .05). The age-specific incidence of HR(+)/HER2(+) and HR(-)/HER2(+) subtypes did not vary markedly between white and black women. The black-white crossover in breast cancer incidence occurs only when all breast cancer subtypes are combined and relates largely to higher rates of triple-negative breast cancers and lower rates of HR(+)/HER2(-) breast cancers in black vs white women.

Analysis of Clinical Features and Outcome of 356 Triple-Negative Breast Cancer Patients in China

Background: The purpose of this study was to investigate the clinicopathological features and analyze the prognostic factors of triple-negative breast cancer (TNBC). Patients and Methods: The clinical data of 1,788 breast cancer patients was collected and analyzed. The Kaplan-Meier method was used to estimate survival. Multivariate analysis of the prognostic factors for survival was performed using the Cox regression model. Results: Patients with TNBC exhibited characteristics significantly differing from those with non-TNBC. There was a higher proportion of patients with age < 35 years, stage III disease, tumor size > 5 cm, lymph node positivity, and histological grade 3. The 5-year disease-free survival (DFS) rates of TNBC and non-TNBC patients were 75.7 and 79.6%, respectively (p < 0.05). 5-year overall survival (OS) was 86.6 and 93.5%, respectively (p < 0.05). In multivariate Cox regression analysis, the independent prognostic factors for shorter DFS were age < 35 years (hazard ratio (HR) 2.105), positive lymph nodes (HR 7.039), histological grade 3 (HR 1.841), and for shorter OS positive lymph nodes (HR 4.626). Conclusion: The proportion of TNBC in breast cancer in China is higher than in other areas. TNBC is correlated with younger age, larger tumor size, positive lymph nodes, higher clinical stage and histological grade, and lower DFS and OS, which is consistent with previous reports.

Reproductive History and Oral Contraceptive Use in Relation to Risk of Triple-Negative Breast Cancer

Triple-negative (ie, estrogen receptor [ER], progesterone receptor, and HER2 negative) breast cancer occurs disproportionately among African American women compared with white women and is associated with a worse prognosis than ER-positive (ER+) breast cancer. Hormonally mediated risk factors may be differentially related to risk of triple-negative and ER+ breast cancers. Using data from 155,723 women enrolled in the Women's Health Initiative, we assessed associations between reproductive and menstrual history, breastfeeding, oral contraceptive use, and subtype-specific breast cancer risk. We used Cox regression to evaluate associations with triple-negative (N = 307) and ER+ (N = 2610) breast cancers and used partial likelihood methods to test for differences in subtype-specific hazard ratios (HRs). Reproductive history was differentially associated with risk of triple-negative and ER+ breast cancers. Nulliparity was associated with decreased risk of triple-negative breast cancer (HR = 0.61, 95% confidence interval [CI] = 0.37 to 0.97) but increased risk of ER+ breast cancer (HR = 1.35, 95% CI = 1.20 to 1.52). Age-adjusted absolute rates of triple-negative breast cancer were 2.71 and 1.54 per 10,000 person-years in parous and nulliparous women, respectively; by comparison, rates of ER+ breast cancer were 21.10 and 28.16 per 10,000 person-years in the same two groups. Among parous women, the number of births was positively associated with risk of triple-negative disease (HR for three births or more vs one birth = 1.46, 95% CI = 0.82 to 2.63) and inversely associated with risk of ER+ disease (HR = 0.88, 95% CI = 0.74 to 1.04). Ages at menarche and menopause were modestly associated with risk of ER+ but not triple-negative breast cancer; breastfeeding and oral contraceptive use were not associated with either subtype. The association between parity and breast cancer risk differs appreciably for ER+ and triple-negative breast cancers. These findings require further confirmation because the biological mechanisms underlying these differences are uncertain.

Higher population‐based incidence rates of triple‐negative breast cancer among young African‐American women

Differences in the breast cancer burden of African-American women compared with white American women are well documented. Recent controversies have emerged regarding age-appropriate mammographic screening guidelines, and these surveillance recommendations may influence future breast cancer disparities. The objective of the current study was to evaluate age-specific breast cancer stage distributions and incidence rates of triple-negative breast cancer (TNBC) in a population-based tumor registry. The authors analyzed breast cancers from the California Cancer Registry (CCR) that were diagnosed between 1988 and 2006. The results were stratified by age and race/ethnicity, with white Americans identified as non-Hispanic whites (NHWs) and African Americans identified as non-Hispanic blacks (NHBs). Breast cancer stage distributions and TNBC incidence rates also were analyzed. In total, 375,761 invasive breast cancers were evaluated (including 276,938 in NHWs and 21,681 in NHBs). NHBs and Hispanics tended to be younger than NHWs (median ages 57 years, 54 years, and 64 years, respectively). Lifetime incidence rates were higher for NHWs compared with NHBs and Hispanics; however, for women aged <44 years, incidence was highest among NHBs. NHBs also had higher incidence rates of stage III and IV disease and a higher incidence of TNBC in all age categories. Population-based data demonstrated that African-American women had a more advanced stage distribution for breast cancer compared with white American women and higher incidence rates for TNBC. These patterns were observed for women ages 40 to 49 years and for older women, and they suggest that mammographic screening for the early detection of breast cancer will be particularly relevant for younger African-American women.

Abstract P1-11-07: Results of a Phase II Study of Neoadjuvant Platinum/Taxane Based Chemotherapy and Erlotinib for Triple Negative Breast Cancer

Abstract Introduction: Patients with triple negative breast cancer (TNBC) have a worse prognosis compared to other breast cancer subtypes, primarily due to lack of targeted treatment options. EGFR1 (epidermal growth factor receptor) is often over-expressed in TNBC and could be a promising therapeutic target. Clinical studies have shown platinums and taxanes to be effective in TNBC and in vitro data has demonstrated synergy between carboplatin, docetaxel and an EGFR inhibitor in TNBC cell lines. Aim: To evaluate the efficacy of platinum/taxane based chemotherapy in combination with a small molecule EGFR inhibitor, Erlotinib, in patients with TNBC. Methods: Patients with stage II/III TNBC were eligible for this phase II trial. All patients received 6 cycles of chemotherapy (Carboplatin AUC 6, Docetaxel 75mg/m2 every 21 d). In addition patients were equally randomized between two erlotinib arms. Patients in arm A received Erlotinib (150 mg PO d 3 - 14 every 21 d) during all 6 cycles of chemotherapy &amp; patients in arm B received erlotinib only during the last 4 cycles of chemotherapy. This randomization was intended to reduce bias in the evaluation of the effect of erlotinib on biomarkers in a core biopsy of the tumor performed after the second cycle of chemotherapy. All but one patient underwent comprehensive BRCA analysis (Myriad Genetic Laboratories). Following neo-adjuvant therapy, all patients underwent breast surgery. The primary end point was pathological complete response (pCR: no evidence of invasive tumor in the breast &amp; axilla). Minimal Residual Disease [MRD= Residual Cancer Burden (RCB) groups 0+1] status was also evaluated. Results: 30 eligible patients with TNBC were enrolled between 8/2007 and 6/2010. This analysis includes 28 patients since 2 patients are still on study treatment. Median age: 51yrs (range 31-68), 21%: African American, 54%: postmenopausal. Median tumor size was 3.3 cm &amp; 39% had LN+ disease. Fifteen patients were assigned to each arm of erlotinib. Five of 28 patients (17%) carried a BRCA mutation (two BRCA1deleterious, two BRCA2 deleterious, one BRCA1 uncertain). The overall pCR and MRD (RCB 0+1) rates were 39% &amp; 50% respectively. On univariate analysis, tumor size, LN status, menopausal status, age and number of erlotinib cycles did not correlate with pCR. However, BRCA mutation status strongly correlated with pCR, with a pCR rate of 100% in BRCA mutation carriers compared to 27% in those without BRCA mutation (p=0.006). Baseline EGFR and/or p53 expression of ≥10% was associated with a lower pCR rate in BRCA non-carriers (pCR: 12% vs. 66%, p = 0.025). Common Erlotinib related AEs were: rash (G3/4:7%) &amp; diarrhea (G3/4:30%) with 32% of subjects requiring erlotinib dose reduction/discontinuation due to AEs. Conclusions: Pathological complete response rates of TNBC to a combination of platinum/taxane chemotherapy &amp; an oral EGFR inhibitor are encouraging and should be explored further. The response to this regimen was significantly influenced by BRCA mutation status, indicating a need to stratify patients by their BRCA status in future TNBC trials. Tissue biomarker analysis of downstream targets of EGFR inhibition should be informative regarding the exact role of erlotinib in this patient population. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P1-11-07.

Racial differences in the incidence of breast cancer subtypes defined by combined histologic grade and hormone receptor status

Breast cancer encompasses several distinct clinical entities of very different characteristics and behaviors, a fact which likely contributes to the higher breast cancer mortality in African-Americans (AA) despite the higher incidence in European-Americans (EA). We are interested in how incidence variability in cancer subtypes defined by combined estrogen receptor (ER) and grade contributes to racial mortality disparities. As an initial step, we compared age-specific and age-adjusted incidence rates for each ER/Grade subtype in South Carolina (SC-a southern state) with Ohio (a northern mid-western state), using state registry data for 1996-2004. Each ER/Grade subtype had a distinct incidence pattern and rate, with three striking racial/geographic differences. First, the racial incidence disparity in ER negative (ER-) cancers was mostly within the ER-/G3 subtype, of which AAs had ~65% higher incidence than did EAs; ER-/G2 was much less common, but of significantly higher incidence in AAs. Second, the racial disparity in ER positive (ER+) cancers was in the ER+/lower-grade cancers, with a marked EA excess in both states. Third, AA incidence of the ER+/lower-grade subtypes was ~26% higher in Ohio than in SC. The other subtypes (ER-/G1 and ER+/G3) varied minimally by race and state, and the latter showed a strong association with age. Age adjustment halved the racial difference in mean age at diagnosis to about 2 years younger in AAs, compared to 4 years younger in case comparisons. Use of age-adjusted and age-specific rates of breast cancer subtypes may improve understanding of racial incidence and mortality disparities over time and geography. This approach also may aid in estimating the race-specific incidence rates of triple-negative breast cancer.