Asian Breast Cancer Patients Research Articles

52247 Prospective cohort study on hair loss and skin alterations in Asian breast cancer patients during treatment"

52247 Prospective cohort study on hair loss and skin alterations in Asian breast cancer patients during treatment"

Higher disease burden and lower utilization in Mongolian with breast cancer: a 9-year retrospective cohort study of 18.19 million adults in China.

Whether health inequalities of disease burden and medical utilization exist by ethnicity in Asian breast cancer (BC) patients remains unclear. The authors aim to measure ethnic disparities in disease burden and utilization among Mongolian and Han female BC patients in China. Based on data extracted from Inner Mongolia Regional Health Information Platform, a retrospective cohort study was established during 2012-2021. Disease burden including incidence, 5-year prevalence, mortality, survival rate, and medical cost were analyzed and compared between Han and Mongolian patients. A total of 34878 female patients [mean (SD) age, 52.34 (10.93) years] were included among 18.19 million Chinese, and 4315 (12.03%) participants were Mongolian. Age-standardized rates of incidence are 32.68 (95% CI: 20.39-44.98) per 100000. Higher age-specific incidence and 5-year prevalence were observed in Mongolian than in Han. The cost of BC annually per capita was significantly lower for Mongolian than Han [$1948.43 (590.11-4 776.42) vs. $2227.35 (686.65-5929.59), P <0.001]. Mongolian females showed higher all-cause mortality [30.92 (95% CI: 28.15-33.89) vs. 27.78 (95% CI: 26.77-28.83) per 1000, P =0.036] and BC-specific mortality [18.78 (95% CI: 16.64-21.13) vs. 15.22 (95% CI: 14.47-16.00) per 1000, P =0.002] than Han females. After adjusting covariates, Mongolian were associated with increased all-cause mortality [HR, 1.21, (95% CI: 1.09-1.34); P <0.001] and BC-specific mortality [HR, 1.31, (95% CI: 1.14-1.49); P <0.001]. The findings of this cohort study highlight a higher level of disease burden with unmet medical demand in Mongolian patients, suggesting that more practical efforts should be made for the minority. Further research is needed to explore the concrete mechanisms of the disparities as well as eliminate health disproportion.

Exploring the effectiveness of molecular subtypes, biomarkers, and genetic variations as first-line treatment predictors in Asian breast cancer patients: a systematic review and meta-analysis

BackgroundBreast cancer incidence has been on the rise significantly in the Asian population, occurring at an earlier age and a later stage. The potential predictive value of molecular subtypes, biomarkers, and genetic variations has not been deeply explored in the Asian population. This study evaluated the effect of molecular subtype classification and the presence or absence of biomarkers and genetic variations on pathological complete response (pCR) after neoadjuvant treatment in Asian breast cancer patients.MethodsA systematic search was conducted in MEDLINE (PubMed), Science Direct, Scopus, and Cochrane Library databases. Studies were selected if they included Asian breast cancer patients treated with neoadjuvant chemotherapy and contained data for qualitative or quantitative analyses. The quality of the included studies was assessed using the Newcastle Ottawa Scale. Following the random effects model, pooled odds ratios or hazard ratios with 95% confidence intervals for pCR were analysed using Review Manager Software. Heterogeneity between studies was assessed using Cochran’s Q-test and I2 test statistics.ResultsIn total, 19,708 Asian breast cancer patients were pooled from 101 studies. In the neoadjuvant setting, taxane-anthracycline (TA) chemotherapy showed better pCR outcomes in triple-negative breast cancer (TNBC) (p<0.0001) and human epidermal growth factor receptor 2 enriched (HER2E) (p<0.0001) than luminal breast cancer patients. Similarly, taxane-platinum (TP) chemotherapy also showed better pCR outcomes in TNBC (p<0.0001) and HER2E (p<0.0001). Oestrogen receptor (ER)-negative, progesterone receptor (PR)-negative, HER2-positive and high Ki-67 were significantly associated with better pCR outcomes when treated with either TA or TP. Asian breast cancer patients harbouring wildtype PIK3CA were significantly associated with better pCR outcomes when treated with TA in the neoadjuvant setting (p=0.001).ConclusionsIn the neoadjuvant setting, molecular subtypes (HER2E and TNBC), biomarkers (ER, PR, HER2, HR, Ki-67, nm23-H1, CK5/6, and Tau), and gene (PIK3CA) are associated with increased pCR rates in Asian breast cancer patients. Hence, they could be further explored for their possible role in first-line treatment response, which can be utilised to treat breast cancer more efficiently in the Asian population. However, it needs to be further validated with additional powered studies.Systematic review registrationPROSPERO CRD42021246295.

Outcomes of whole breast radiation therapy in Asian breast cancer patients with prior cosmetic implants.

As breast augmentation has become more popular, an increasing number of women with augmented breasts require treatment for breast cancer. This study aimed to assess the outcomes of postoperative whole breast radiation therapy (WB-RT) in Asian patients with breast cancer who underwent prior cosmetic breast implantation. We retrospectively reviewed the medical records of 61 patients with breast cancer who had prior cosmetic breast implants (prior-CBI) and underwent breast-conserving surgery (BCS) and WB-RT between 2015 and 2020. The median implant volume was 238.8cc, with a median interval of 84.7months between the prior-CBI and BCS. WB-RT was administered with either conventional fractionation (CF-RT) at 50Gy in 25 fractions (N = 36) or hypofractionation (HF-RT) at 42.6Gy in 16 fractions (N = 25). The incidences of implant-related complications (IRC) and their contributing factors were analyzed. After a median follow-up of 43.5months, the 3-year cumulative incidences of IRC and implant loss were 17.2% and 4.9%, respectively. Among the four (6.6%) patients who opted for implant removal after RT, three were potentially related to RT-related capsular contracture. There was no difference in the 3-year cumulative IRC rates following CF-RT and HF-RT (12.2% and 26.7%, respectively; p = 0.120). The risk factors for IRC included a larger implant size (> 260cc) and a higher ratio of breast tissue to implant volume. This study demonstrated a favorable safety profile of WB-RT for treatment of breast cancer in Asian women with prior-CBI. The integration of HF-RT following BCS was thought to be a feasible approach.

Assessment of hair loss and skin changes during treatment in Asian breast cancer patients: A prospective cohort study.

With the increasing number of young breast cancer (BC) patients worldwide, concerns about hair loss and skin change persist among BC survivors. This study aimed to evaluate the hair loss and skin changes in Asian BC patients and to compare them according to the treatment regimens. This study enrolled 322 patients scheduled to undergo BC surgery. Hair loss and skin changes were assessed at the following two time points: one day before surgery and 6 months after surgery. Patients who had received systemic anticancer treatment before surgery were assigned to the neoadjuvant treatment group, while patients who were scheduled to receive systemic anticancer treatment were assigned to the adjuvant treatment group. In the adjuvant treatment group, patients with taxane-based chemotherapy had significantly higher odds of increased hair loss, a higher melanin index, and an increased volume of wrinkles (p < 0.0001, p = 0.0110, and p = 0.0371, respectively). In the neoadjuvant treatment group, hair loss was reversed in most patients at 6 months after surgery. Clinicians should inform BC patients about the potential for hair loss and skin changes and provide supportive care to mitigate the effects on the patients' quality of life.

Conventional standard-sized bra with prosthesis or patient’s bra with customized hand-knitted external prosthesis after mastectomy: Mixed-methods evaluation of patients’ preferences

INTRODUCTION: In breast cancer patients undergoing mastectomy without reconstruction, an external breast prosthesis could aid patients’ recovery, improve body image and confidence by helping to regain a symmetrical chest appearance when dressed. However, external breast prosthesis preferences among Asian breast cancer patients were not widely studied. We aimed to compare patients’ experience with the conventional commercially manufactured standard-sized (small, medium, large, extra-large) bra and prosthesis versus customized hand-knitted external breast prosthesis with patient’s bra after unilateral mastectomy at a tertiary hospital. This is the first such study in Asian women, to our knowledge. METHODS: In this prospective study, participants used the conventional bra-prosthesis followed by the customized one consecutively, each for at least 3 months before they were administered an identical questionnaire at 3 and 6 months respectively. The questionnaire assessed the patients’ experience with the prosthesis on the aspects of comfort, body image and satisfaction etc. Patients were also invited for in-depth interviews. RESULTS: Of 155 eligible patients, 148 patients participated with a response rate of 95.5%. 99 (67%) participants preferred the customized prosthesis, while 38 (25.7%) did not. 11 (7.4%) participants were undecided. Seventeen participants underwent in-depth interviews until data saturation on major qualitative themes was achieved. More patients experienced excessive sweating (p &lt; 0.0001), greater discomfort (p = 0.0195) and higher rates of prosthesis dislodgement (p = 0.0269) with the conventional bra-prosthesis. CONCLUSION: Customized external breast prostheses could be an alternative to the conventional ones for breast cancer patients with mastectomy, with additional benefits of less sweating, more comfort and less dislodgement perceived.

Abstract C031: ABCD3 expression is upregulated Caucasian and Asian breast cancer patients and is associated with non-responsiveness to endocrine therapy in luminal breast cancers

Abstract The ABC transporters represent the largest family of transmembrane proteins. They also serve in protective roles whereby many transporters act as efflux pumps for xenobiotics. And subsequently, several members; most notably of the A, B and C subfamilies, have been implicated in cancer chemoresistance; however, D family members have not been extensively studies with regards to cancer biology and treatment. Here we report that ABCD3 transporter expression is upregulated in breast cancer (p&amp;lt;0.001). The gene was also upregulated across cancer stages (p&amp;lt;0.05). Analysis of histological subtypes revealed that ABCD3 was expressed infiltrating ductal carcinoma (IDC). Immunohistochemistry (IHC) analysis confirmed that ABCD3 protein is expressed IDC (p&amp;lt;0.001). Moreover, ABCD3 expression was elevated in White (p&amp;lt;0.001) and Asian (p&amp;lt;0.05) breast cancer patients but not in African-American patients. Analysis of molecular subtypes revealed that ABCD3 expression was significantly higher in the Luminal breast cancer subtype (p&amp;lt;0.001). Furthermore, ROC analysis of gene expression in relationship in response to treatment revealed that ABCD3 is a moderate predictor (AUC=0.644, p=0.003) of response to endocrine therapy (tamoxifen and aromatase inhibitors) and a strong predictor (AUC=08, p=0.026) to chemotherapy in luminal breast cancers. Taken collectively, ABCD3 represents a biomarker which may be important for determining therapeutic response. Citation Format: Romonia Renee Reams, Simone Heyliger, Marilyn Saulsbury. ABCD3 expression is upregulated Caucasian and Asian breast cancer patients and is associated with non-responsiveness to endocrine therapy in luminal breast cancers [abstract]. In: Proceedings of the 16th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2023 Sep 29-Oct 2;Orlando, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2023;32(12 Suppl):Abstract nr C031.

How Asian Breast Cancer Patients Experience Unequal Incidence of Chemotherapy Side Effects: A Look at Ethnic Disparities in Febrile Neutropenia Rates.

The majority of published findings on chemotherapy-induced febrile neutropenia (FN) are restricted to three ethnic groups: Asians, Caucasians, and African Americans. In this two-part study, we examined FN incidence and risk factors in Chinese, Malay, and Indian chemotherapy-treated breast cancer (BC) patients. Hospital records or ICD codes were used to identify patients with FN. In both the Singapore Breast Cancer Cohort (SGBCC) and the Joint Breast Cancer Registry (JBCR), the time of the first FN from the start of chemotherapy was estimated using Cox regression. Multinomial regression was used to evaluate differences in various characteristics across ethnicities. FN was observed in 170 of 1014 patients in SGBCC. The Cox model showed that non-Chinese were at higher risk of developing FN (HRMalay [95% CI]:2.04 [1.44-2.88], p < 0.001; HRIndian:1.88 [1.11-3.18], p = 0.018). In JBCR, FN was observed in 965 of 7449 patients. Univariable Cox models identified ethnicity, a lower baseline absolute neutrophil count, non-luminal A proxy subtypes, and anthracycline-containing regimens as risk factors. Disparities across ethnicities' risk (HRMalay:1.29 [1.07-1.54], p = 0.006; HRIndian:1.50 [1.19-1.88], p < 0.001) remained significant even after further adjustments. Finally, an age-adjusted multinomial model showed that Malays (p = 0.006) and Indians (p = 0.009) were significantly more likely to develop multiple episodes of FN during treatment. Ethnic differences in chemotherapy-induced FN among BC patients exist. Further studies can focus on investigating pharmacogenetic differences across ethnicities.

Survival outcomes of young patients under 40 with breast cancer in Asian countries according to subtype: An international multicenter cohort study.

562 Background: The incidence of young Asian women with breast cancer has been increasing but these patients are underrepresented in global data. We analyzed the epidemiology and outcomes of the young Asian patients with breast cancer in different subtypes with clinically unmet need. Methods: Female patients of age 20 years or older diagnosed with early breast cancer of stage I, II, or III from the prospective cohort of the Asian Breast Cancer Cooperative Group (ABCCG) were analyzed. For comparison, data of patients with early breast cancer from Surveillance, Epidemiology, and End Results Program (SEER) cancer registry was used. The patients were divided into three age groups: young (below 40 years), alleged premenopausal mid-age (40-49 years), and alleged postmenopausal elderly (50 years and older). Multivariable Cox proportional-hazard models for survivals were adjusted with age, subtypes consisting of hormone receptor (HR) and human epithelial growth factor receptor 2 (HER2) status, histologic grade, T stage, nodal status, and countries. Patients diagnosed in 2000–2010 were censored at 6 years for comparability with SEER database. Results: Total 45,021 patients with breast cancer from Asian countries, 496,332 of SEER Whites and 18,279 from SEER non-Whites were included. The median age at diagnosis was younger in Asians compared to SEER Whites and non-Whites (51, 62, 58 years, respectively). Among subtypes, HR-positive and HER2-negative breast cancer was more frequent among SEER Whites and SEER non-Whites, compared to Asians (75.89%, 73.38% vs. 65.75%, respectively). In the young group, HR-positive and HER2-negative breast cancer was prevalent in Asians and SEER non-Whites, compared to SEER Whites (61.2% and 59.8% vs. 54.7%, respectively). In the elderly group, the proportion of HR-positive breast cancer increased in SEER Whites, while that of triple-negative breast cancer (TNBC) increased in Asians. Elderly group showed the worst survival in all subtypes and in all populations. In Asian population, the mid-age group of the patients with HR-positive and HER2-negative breast cancer showed significantly superior overall survival (OS) than the young group (6 year OS 96.6% vs. 94.4%; hazard ratio 0.62, 95% confidence interval 0.50-0.76; p&lt;0.001). Similarly, young patients in SEER Whites also showed early decline of survival curve compared those in mid-age group (89.1% vs. 94.0%, p&lt;0.001), while young patients of SEER non-Whites showed equivalent prognosis to those in mid-age group (92.4% vs. 95.0%, p=0.118). Conclusions: Young Asian breast cancer patients diagnosed with HR-positive and HER2-negative subtypes, but not HER2-positive or TNBC subtypes, are more likely to have worse survival outcomes than those in mid-age. Further studies on young patients with breast cancer are needed for tailored treatments among different subtypes and ethnic groups.

TP53 somatic mutations in Asian breast cancer are associated with subtype-specific effects

BackgroundRecent genomics studies of breast cancer in Asian cohorts have found a higher prevalence of TP53 mutations in Asian breast cancer patients relative to Caucasian patients. However, the effect of TP53 mutations on Asian breast tumours has not been comprehensively studied.MethodsHere, we report an analysis of 492 breast cancer samples from the Malaysian Breast Cancer cohort where we examined the impact of TP53 somatic mutations in relation to PAM50 subtypes by comparing whole exome and transcriptome data from tumours with mutant and wild-type TP53.ResultsWe found that the magnitude of impact of TP53 somatic mutations appears to vary between different subtypes. TP53 somatic mutations were associated with higher HR deficiency scores as well as greater upregulation of gene expression pathways in luminal A and luminal B tumours compared to the basal-like and Her2-enriched subtypes. The only pathways that were consistently dysregulated when comparing tumours with mutant and wild-type TP53 across different subtypes were the mTORC1 signalling and glycolysis pathways.ConclusionThese results suggest that therapies that target TP53 or other downstream pathways may be more effective against luminal A and B tumours in the Asian population.

Abstract P4-07-49: Neoadjuvant therapy in Asian breast cancer patients with early &amp; locally advanced breast cancers – A contemporary experience from a large tertiary hospital in Singapore

Abstract Background: Non-metastatic breast cancers (BC) are increasing treated with neoadjuvant therapy (NAT). Complete pathological response (pCR) is associated with improved survival. Early identification of care needs during NAT is crucial. We report our institution’s experience with NAT. Methods: A prospectively recruited cohort diagnosed with BC, referred to NAT program at SingHealth acute hospitals between June 2020 and June 2021. Demographics, clinical data, pCR (absence of invasive carcinoma in breast and axilla), and Functional Assessment of Cancer Therapy Breast (FACT-B) as quality of life (QOL) measure were collected. Definition of young BC (YBC) were ≤40 years, older adults (OA) ≥65 years. Results: Among 119 eligible patients, 7 (6%) were clinically stage 1, 71 (60%) stage 2, and 41 (35%) stage 3. Twenty-eight (24%) were triple negative (TNBC; defined as HER2- hormonal receptor 0-10% [HR-]), 26 (22%) HER2+ HR-, 45 (38%) HER2+ HR+, 20 (17%) HER2- HR+. Among 71 HER2+ BC, two-thirds received anthracycline (A) based chemotherapy, a quarter A-sparing and remaining 9% taxane only. Majority (89%) received dual HER2 blockade. Among TNBC, 28 (71%) received additional platinum and 2 (7%) immunotherapy. Majority (77%; n=92) completed NAT. Toxicity was main reason for incompletion. Three patients did not undergo surgery: 1 defaulted, 1 demised and the last patient’s surgery was not due at analysis. Of the 116 who underwent surgery, 23 (20%) had breast conservation and 93 (80%) mastectomy. Forty-nine (42%) achieved pCR - 12 (43%) TNBC, 17 (65%) HER2+ HR-, 20 (44%) HER2+ HR+ and 0 in HER2- HR+ (p &amp;lt; 0.001). The pCR rates were also lower by increasing age (Multivariable OR 0.93; 95% CI, 0.90-0.97). Baseline median FACT-B scores was 117 (IQR 102-126) for the cohort: 108 for YBC, 116 for OA and 120 for the rest (p=0.200). At baseline, median score was 28, 24, 18, 22 and 27 in physical, social, emotional, functional wellbeing and BC subscale, respectively, and YBC and OA patients had lower social wellbeing scores than the remaining cohort (22 vs 24, p=0.011). Conclusion: Highest pCR were observed with HER2+ followed by TNBC. Pre-operatively, FACT-B scores were comparable by demographics, staging and tumor subtypes. However, care must be paid to social wellbeing for women in age extremes undergoing NAT. Citation Format: Zewen Zhang, Jun Ma, Jasmine Yun Ting Tan, Whee Sze Ong, Sulastri Kamis, Grace Yang, Benita Kiat Tee Tan, Veronique Kiak Mien Tan, Tira J. Tan. Neoadjuvant therapy in Asian breast cancer patients with early &amp; locally advanced breast cancers – A contemporary experience from a large tertiary hospital in Singapore [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P4-07-49.

Mammographic Density Reduction is Associated to the Prognosis in Asian Breast Cancer Patients Receiving Hormone Therapy.

Using mammographic density as a significant biomarker for predicting prognosis in adjuvant hormone therapy patients is controversial due to the conflicting results of recent studies. This study aimed to evaluate hormone therapy-induced mammographic density reduction and its association with prognosis in Taiwanese patients. In this retrospective study, 1941 patients with breast cancer were screened, and 399 patients with estrogen receptor-positive breast cancer who received adjuvant hormone therapy were enrolled. The mammographic density was measured using a fully automatic estimation procedure based on full-field digital mammography. The prognosis included relapse and metastasis during treatment follow-up. The Kaplan-Meier method and Cox proportional hazards model were used for disease-free survival analysis. A mammographic density reduction rate >20.8%, measured preoperatively and after receiving hormone therapy from 12-18 months, was a significant threshold for predicting prognosis in patients with breast cancer. The disease-free survival rate was significantly higher in patients whose mammographic density reduction rate was >20.8% (P = .048). This study's findings could help estimate the prognosis for patients with breast cancer and may improve the quality of adjuvant hormone therapy after enlarging the study cohort in the future.

Mammography screening is associated with more favourable breast cancer tumour characteristics and better overall survival: case-only analysis of 3739 Asian breast cancer patients

BackgroundEarly detection of breast cancer (BC) through mammography screening (MAM) is known to reduce mortality. We examined the differential effect that mammography has on BC characteristics and overall survival and the sociodemographic determinants of MAM utilization in a multi-ethnic Asian population.MethodsThis study included 3739 BC patients from the Singapore Breast Cancer Cohort (2010–2018). Self-reported sociodemographic characteristics were collected using a structured questionnaire. Clinical data were obtained through medical records. Patients were classified as screeners (last screening mammogram ≤ 2 years before diagnosis), non-screeners (aware but did not attend or last screen > 2years), and those unaware of MAM. Associations between MAM behaviour (MB) and sociodemographic factors and MB and tumour characteristics were examined using multinomial regression. Ten-year overall survival was modelled using Cox regression.ResultsPatients unaware of screening were more likely diagnosed with late stage (ORstage III vs stage I (Ref) [95% CI]: 4.94 [3.45–7.07], p < 0.001), high grade (ORpoorly vs well-differentiated (reference): 1.53 [1.06–2.20], p = 0.022), nodal-positive, large size (OR>5cm vs ≤2cm (reference): 5.06 [3.10–8.25], p < 0.001), and HER2-positive tumours (ORHER2-negative vs HER2-positive (reference): 0.72 [0.53–0.97], p = 0.028). Similar trends were observed between screeners and non-screeners with smaller effect sizes. Overall survival was significantly shorter than screeners in the both groups (HRnon-screeners: 1.89 [1.22–2.94], p = 0.005; HRunaware: 2.90 [1.69–4.98], p < 0.001).Non-screeners and those unaware were less health conscious, older, of Malay ethnicity, less highly educated, of lower socioeconomic status, more frequently ever smokers, and less physically active. Among screeners, there were more reported personal histories of benign breast surgeries or gynaecological conditions and positive family history of breast cancer.ConclusionsMammography attendance is associated with more favourable BC characteristics and overall survival. Disparities in the utility of MAM services suggest that different strategies may be needed to improve MAM uptake.

Association of Pathway Mutations With Survival in Taiwanese Breast Cancers.

Breast cancer is the most common invasive cancer in women worldwide. Next-generation sequencing (NGS) provides a high-resolution profile of cancer genome. Our study ultimately gives the insight for genetic screening to identify the minority of patients with breast cancer with a poor prognosis, who might benefit from the most intensive possible treatment. The detection of mutations can polish the traditional method to detect high-risk patients who experience poor prognosis, recurrence and death early. In total, 147 breast cancer tumors were sequenced with targeted sequencing using a RainDance Cancer Hotspot Panel. The average age of all 147 breast cancer patients in the study was 51.7 years, with a range of 21–77 years. The average sequencing depth was 5,222x (range 2,900x-8,633x), and the coverage was approximately 100%. A total of 235 variants in 43 genes were detected in 147 patients by high-depth Illumina sequencing. A total of 219 single nucleotide variations were found in 42 genes from 147 patients, and 16 indel mutations were found in 13 genes from 84 patients. After filtering with the 1000 Genomes database and for synonymous SNPs, we focused on 54 somatic functional point mutations. The functional point mutations contained 54 missense mutations in 22 genes. Additionally, mutation of genes within the RET, PTEN, CDH1, MAP2K4, NF1, ERBB2, RUNX1, PIK3CA, FGFR3, KIT, KDR, APC, SMO, NOTCH1, and FBXW7 in breast cancer patients were with poor prognosis. Moreover, TP53 and APC mutations were enriched in triple-negative breast cancer. APC mutations were associated with a poor prognosis in human breast cancer (log-rank P<0.001). Our study identified tumor mutation hotspot profiles in Taiwanese breast cancer patients, revealing new targetable gene mutations in Asian breast cancer patients.

Impact of contrast-enhanced mammography in surgical management of breast cancers for women with dense breasts: a dual-center, multi-disciplinary study in Asia

ObjectiveTo evaluate the impact of pre-operative contrast-enhanced mammography (CEM) in breast cancer patients with dense breasts.MethodsWe conducted a retrospective review of 232 histologically proven breast cancers in 200 women (mean age: 53.4 years ± 10.2) who underwent pre-surgical CEM imaging across two Asian institutions (Singapore and Taiwan). Majority (95.5%) of patients had dense breast tissue (BI-RADS category C or D). Surgical decision was recorded in a simulated blinded multi-disciplinary team setting on two separate scenarios: (i) pre-CEM setting with standard imaging, and clinical and histopathological results; and (ii) post-CEM setting with new imaging and corresponding histological findings from CEM. Alterations in surgical plan (if any) because of CEM imaging were recorded. Predictors CEM of patients who benefitted from surgical plan alterations were evaluated using logistic regression.ResultsCEM resulted in altered surgical plans in 36 (18%) of 200 patients in this study. CEM discovered clinically significant larger tumor size or extent in 24 (12%) patients and additional tumors in 12 (6%) patients. CEM also detected additional benign/false-positive lesions in 13 (6.5%) of the 200 patients. Significant predictors of patients who benefitted from surgical alterations found on multivariate analysis were pre-CEM surgical decision for upfront breast conservation (OR, 7.7; 95% CI, 1.9-32.1; p = 0.005), architectural distortion on mammograms (OR, 7.6; 95% CI, 1.3–42.9; p = .022), and tumor size of ≥ 1.5 cm (OR, 1.5; 95% CI, 1.0-2.2; p = .034).ConclusionCEM is an effective imaging technique for pre-surgical planning for Asian breast cancer patients with dense breasts.Key Points• CEM significantly altered surgical plans in 18% (nearly 1 in 5) of this Asian study cohort with dense breasts.• Significant patient and imaging predictors for surgical plan alteration include (i) patients considered for upfront breast-conserving surgery; (ii) architectural distortion lesions; and (iii) tumor size of ≥ 1.5 cm.• Additional false-positive/benign lesions detected through CEM were uncommon, affecting only 6.5% of the study cohort.

Genetic ancestry correlates of the cancer somatic mutational landscape from tumor profiling data of 50,000 patients with cancer.

10573 Background: The incidence and mortality of cancer vary widely across race and ethnicity. This is attributed to an interplay of socioeconomic factors, environmental exposures, and genetic background. Cancer genomic studies have underrepresented minorities and individuals of non-European descent, thus limiting a comprehensive understanding of disparities in the diagnosis, prognosis, and treatment of cancer among these populations. Furthermore, the social constructs of race and ethnicity are far from precise categories to understand the biological underpinnings of such differences. In this study, we use a large real-world data (RWD) patient cohort to examine associations of genetic ancestry with somatic alterations in known cancer driver genes. Methods: We inferred genetic ancestry from approximately 50,000 de-identified records from cancer patients of diverse histology who underwent tumor genomic profiling with the Tempus xT next-generation sequencing (NGS) assay. Our cohort includes patients with brain, breast, colorectal, hematopoietic, lung, and ovarian cancers, among others. We used 654 ancestry informative markers selected to overlap the target regions of the 648-gene Tempus xT NGS assay to infer global ancestry proportions at the continental level: Africa (AFR), America (AMR), Europe (EUR), East Asia (EAS), and South Asia (SAS). We imputed race/ethnicity categories using ancestry proportions on subjects lacking such metadata. Results: Most patients were of European descent (72%), however, continental genetic ancestry inference identified 4.7 and 3.8-fold more patients with substantial (&gt; 50%) AFR and AMR ancestry, correspondingly, compared with TCGA. We observed higher percentages of AFR ancestry patients with prostate, breast, and colorectal cancer (1.8-3.1%) and AMR ancestry patients with colorectal cancer (2.4%) compared to the overall cohort-level distributions (p &lt; 0.05). Using imputation, we identified 60% and 121% more patients as likely Black and Hispanic/Latino, respectively. We observed several associations between genetic ancestry with tumor mutation burden (TMB), e.g., a reduction in median TMB in Asian breast cancer patients (Asian TMB mean = 2.3 m/Mb vs 4.4 for Black, 3.3 for Hispanic, and 4.2 for White; p &lt; 0.0001), in paired tumor/normal sequencing data. Furthermore, we found associations between ancestry and nonsynonymous somatic mutations in cancer genes, e.g. in CTNNB1 with EAS ancestry (OR = 1.18) and EGFR with EAS (OR = 1.24), AMR (OR = 1.30), and EUR (OR = 0.89) ancestries (all p &lt; 0.001) in lung cancer patients. Conclusions: Our results support the use of genetic ancestry inference on RWD to improve upon the social constructs of race and ethnicity, allowing us to better understand the impact of shared germline genetic or exposure backgrounds into cancer mutational processes that influence incidence, progression, and outcomes.

Mammography screening is associated with more favorable breast cancer tumor characteristics and better overall survival: Case-only analysis of 3,739 Asian breast cancer patients.

e22500 Background: Early detection of breast cancer (BC) through mammography screening (MAM) is known to reduce mortality. We examined the differential effect that mammography has on BC characteristics and overall survival and the sociodemographic determinants of MAM utilisation in a multi-ethnic Asian population. Methods: This study included 3,739 BC patients from the Singapore Breast Cancer Cohort (2010–2018). Self-reported socio-demographic characteristics were collected using a structured questionnaire. Clinical data were obtained through medical records. Patients were classified as screeners (last screening mammogram ≤two years before diagnosis), non-screeners (aware but did not attend or last screen &gt; 2years) and those unaware of MAM. Associations between MAM behaviour (MB) and sociodemographic factors and MB and tumour characteristics were examined using multinomial regression. Ten-year overall survival was modelled using Cox regression. Results: Patients unaware of screening were more likely diagnosed with late stage (ORstage III vs stage I(Ref) [95%CI]:4.94[3.45-7.07], p &lt; 0.001), high grade (ORpoorly- vs well-differentiated(reference): 1.53 [1.06-2.20], p = 0.022), nodal-positive, large size (OR&gt; 5cm vs ≤2cm(reference): 5.06 [3.10-8.25], p &lt; 0.001), and HER2-positive tumors (ORHER2-negative VS -positive(reference): 0.72[0.53-0.97], p = 0.028). Similar trends were observed between screeners and non-screeners with smaller effect sizes. Overall survival was significantly shorter than screeners in the both groups(non-screeners HR: 1.89 [1.22-2.94], p = 0.005; unaware HR: 2.90[1.69-4.98], p &lt; 0.001). Non-screeners and those unaware were less health-conscious, older, of Malay ethnicity, less highly educated, of lower socioeconomic status, more frequently ever smokers and less physically active. Among screeners, there were more reported personal histories of benign breast surgeries or gynaecological conditions and positive family history of breast cancer. Conclusions: Mammography attendance is associated with more favourable BC characteristics and overall survival. Disparities in the utility of MAM services suggest that different strategies may be needed to improve MAM uptake.

Ethnic disparities in adverse events of radiotherapy for breast cancer: A scoping review.

e18502 Background: Ethnic disparities have been well-documented in the US as a contributor to poor outcomes following radiotherapy in ethnic minorities. The objective was to examine the intra-group and inter-group ethnic differences in adverse effects experienced by Asian breast cancer patients undergoing radiotherapy. Methods: A scoping review involving the Pubmed database was conducted. The search strategy included a combination of keywords and index terms related to Asians, breast cancer, CTCAE and treatment. Title, abstract and then full-text screening was performed by two reviewers. Primary research studies and systematic review articles involving female adults in peer-reviewed articles or grey literature records, of any design or date and published in English, were included. Descriptive statistics and charting was used to summarize the results. Results: Of 1765 abstracts retrieved and screened, 37 articles were ultimately included for analysis. The majority of the studies involved Japanese patients (40.5%) followed by Chinese patients (24.3%) with an average of 468 patients being studied per study (ranging from 1-4,869 patients). Only a single study was conducted in the US. 35.1% of studies reported ethnicity and 64.8% of studies reported Asian ethnic subgroups. Most patients underwent whole-breast irradiation (62.1%). 37.5% of studies involved patients with TNM stages I-III breast cancer. Most patients were postoperatively enrolled after BCS (59.4%).ER/PR status was reported in most studies (54.1%) with an average of 553 patients being positive for either hormone receptor and averages of 210 and 905 patients each in studies where numbers were reported individually. HER-2 status was reported in 48.7% of studies with an average of 28 positive HER-2 patients in each study. Most studies reported skin toxicity following radiotherapy (81.1%), commonly grade 1 or 2 (40.5% each) affecting an average of 46% of patients in each study. These dermatological adverse events were radiation dermatitis, hyperpigmentation, fibrosis, hypertrophic scarring or erythema. Conclusions: Ethnicity was under-reported in the studied literature involving breast cancer treatment. Strategies to improve reporting of ethnic subgroups in literature and to reduce psychosocial barriers to access and treatment with a specific focus on mitigating dermatological adverse events of radiotherapy in Asian breast cancer patients may improve overall outcomes in this group.

Ethnic disparities in adverse events of chemotherapy for breast cancer: A scoping review.

e18524 Background: Ethnic disparities may contribute to a higher symptom burden of adverse events following chemotherapy and poorer response to treatment for breast cancer. The objective was to examine the intra-group and inter-group ethnic differences in adverse effects experienced by Asian breast cancer patients undergoing chemotherapy with aromatase inhibitors or tamoxifen. Methods: A scoping review involving the Pubmed database was conducted. The search strategy included a combination of keywords and index terms related to Asians, breast cancer, CTCAE and treatment. Title, abstract and then full-text screening was performed by two reviewers. Primary research studies and systematic review articles involving female adults in peer-reviewed articles or grey literature records, of any design or date and published in English, were included. Descriptive statistics and charting was used to summarize the results. Results: Of 1765 abstracts retrieved and screened, 56 articles were ultimately included for analysis. Most articles (58.9%) studied the adverse events of tamoxifen. The majority of the studies involved Japanese patients (35.7%) followed by Chinese patients (19.6%) with an average of 8515 patients being studied per study. Only 2 studies were conducted in the US. Half the studies (50%) involved patients with TNM stage I breast cancer, postoperatively enrolled after BCS or mastectomy (71.4%). ER/PR status was reported in 58.9% of studies with an average of 494 patients being positive for either hormone receptor. HER-2 status was reported in 10 studies with an average of 53 positive HER-2 patients. 28.5% of studies involved patients with musculoskeletal adverse events following chemotherapy with aromatase inhibitors, commonly grade 3 or above (31.2%). These adverse events were arthralgia, fractures, osteoporosis or myalgia, affecting an average of 33.9% of patients in each study. 35.7% of studies involved patients with endocrinological adverse events following chemotherapy with tamoxifen. These adverse events involved menopausal symptoms, gynecological complications or endometrial cancer, affecting an average of 36.1% of patients in each study. Conclusions: Multi-level differences may contribute to the adverse events affecting Asian breast cancer patients undergoing chemotherapy with aromatase inhibitors or tamoxifen. Improving physician knowledge of ethnic disparities in adverse events occurring in Asian ethnic subgroups can help improve overall outcomes and patient adherence through a patient-centered approach.

Overlap of high-risk individuals predicted by family history, and genetic and non-genetic breast cancer risk prediction models: implications for risk stratification

BackgroundFamily history, and genetic and non-genetic risk factors can stratify women according to their individual risk of developing breast cancer. The extent of overlap between these risk predictors is not clear.MethodsIn this case-only analysis involving 7600 Asian breast cancer patients diagnosed between age 30 and 75 years, we examined identification of high-risk patients based on positive family history, the Gail model 5-year absolute risk [5yAR] above 1.3%, breast cancer predisposition genes (protein-truncating variants [PTV] in ATM, BRCA1, BRCA2, CHEK2, PALB2, BARD1, RAD51C, RAD51D, or TP53), and polygenic risk score (PRS) 5yAR above 1.3%.ResultsCorrelation between 5yAR (at age of diagnosis) predicted by PRS and the Gail model was low (r=0.27). Fifty-three percent of breast cancer patients (n=4041) were considered high risk by one or more classification criteria. Positive family history, PTV carriership, PRS, or the Gail model identified 1247 (16%), 385 (5%), 2774 (36%), and 1592 (21%) patients who were considered at high risk, respectively. In a subset of 3227 women aged below 50 years, the four models studied identified 470 (15%), 213 (7%), 769 (24%), and 325 (10%) unique patients who were considered at high risk, respectively. For younger women, PRS and PTVs together identified 745 (59% of 1276) high-risk individuals who were not identified by the Gail model or family history.ConclusionsFamily history and genetic and non-genetic risk stratification tools have the potential to complement one another to identify women at high risk.