Young Breast Cancer Research Articles

PO-1110 Local control in hypofractionated RT after breast-conservative surgery among young Egyptian patients

Purpose or Objective Since the beginning of coronavirus disease (COVID-19), there is a compelling reason for the use of hypofractionated radiotherapy (HFRT) schedules in cancer management to safeguard the patients and the treating physicians. However, conflicting data shows that young breast cancer (BC) patients have a higher locoregional relapse after breast-conservative surgery (BCS). Given this, we aim to compare the locoregional control between conventional radiotherapy (CRT) and HFRT after BCS in a cohort of young BC patients. Materials and Methods We retrospectively reviewed stage I-III BC patients in two centers diagnosed between 2008 and 2017 who underwent BCS and had follow-up data. Patients were categorized into two groups: CRT (50Gy in 25 fractions) vs. HFRT (40.5 - 42.5 Gy in 15-16 fractions). Boost was added to all patients. Results 247 patients were included in this analysis. Among them, 87 (35%) received CRT, while 160 (65%) were treated by HFRT. The clinicopathological characteristics of CRT vs. HFRT were as follows: The majority of the patients were T1 and T2, 92% in CRT vs. 94% in HFRT. N3 was rare in both groups, 8.3% vs. 5.1% in CRT vs. HFRT, respectively. The CRT had more stage 3 patients than HFRT, 35% vs. 23% respectively, but fewer stage 1 (18.1 vs. 23.5%, respectively). Estrogen/progesterone receptor (ER/PR) positive was 79.5% vs. 76.7%, HER2 enriched was 7% vs. 5%, while high Ki-67 was 56.3% vs. 71.4% in CRT vs. HFRT, respectively. Lymphovascular invasion was positive in 52.7% of CRT vs. 64.3% in HFRT, while the extracapsular extension was positive in 31% of CRT vs. 19.4% in HFRT. The distribution of tumor grades was similar across the groups. After a median follow up of 42 months (range: 5-135), 10% of the total 247 patients developed locoregional recurrences:13.8% (n=12) were in CRT group, whereas 8.1% (n=13) in HFRT, p = 0.158;the HFRT group had insignificant lower locoregional recurrences. In univariate and multivariate analysis, only very young age was an independent poor prognostic factor for locoregional failure. Conclusion We found no significant differences in locoregional control between CRT and the HFRT following BCS among young BC patients. In this COVID-19 pandemic, HFRT should also be considered in young BC patients to shorten the treatment time.

Young Breast Cancer: Novel Gene Methylation in WBC.

Introduction:Breast cancer is a highly diverse disease, and epigenomic alterations, as principle changes in the pathogenesis of breast cancer, have recently been noticed in epimarker research on peripheral blood. Methods:In this study, DNA samples isolated from the white blood cells of 30 breast cancer patients were compared to 30 healthy controls using methylated DNA immunoprecipitation microarray (MeDIP-chip) to determine differentially methylated region as a potential epimarker in cancer and control cases. Results:A total of 1799 differentially methylated regions were identified, including ZNF154, BCL9, and HOXD9, in which significant methylation differences were confirmed in breast cancer patients through a quantitative real-time polymerase chain reaction. Differential methylation of the mentioned genes has been reported in different cancer tissues and cell-free DNA, including breast cancer. Methylation of those genes listed in the white blood cells of our young patients not only relates to their importance in the pathogenesis of breast cancer but may also highlight their potential as primary epimarkers that can warrant further evaluation in large cohort studies. It is important to note that methylation alteration in WBC, as well as genetic mutation, can be identified years before cancer development, which emphasizes this issue as a potential screening marker.

Construction and Validation of a Nomogram to Predict Overall Survival in Very Young Female Patients with Curatively Resected Breast Cancer.

PurposeYoung age is an independent negative predictor of breast cancer (BC) survival and correlates with the risk of local recurrence and contralateral BC. We aimed to design an effective and comprehensive nomogram to predict prognosis in very young patients with curatively resected BC.MethodsFemale patients with a diagnosis of BC aged ≤35 years at presentation were identified from the SEER database as a training cohort. The validation cohort consisted of 1002 consecutive women with BC aged ≤35 years that had received curative resection for BC at the Sun Yat-sen University Cancer Center. A nomogram was built based on the identified variables in multivariate Cox proportional hazards model. The performance of the nomogram was quantified using Harrell’s concordance index (C-index) and calibration curves.ResultsOverall, 10,872 young female patients who underwent surgery for BC were enrolled in the training cohort, while 1002 very young female BC patients were identified as independent validation cohort. Eight covariables (age, race, grade; ER, PR, and HER2 status; T, and N stages) were identified and incorporated to construct a nomogram. The C-index values of the nomogram were 0.727 (95% CI: 0.714–0.740) and 0.722 (95% CI: 0.666–0.778) for OS in the training and validation cohorts, respectively. The calibration curves showed a high degree of agreement between the predicted and actual observed survival rates in both training and validation cohorts. The nomogram displayed good calibration and acceptable discrimination. Based on the TPS of the nomogram model for OS with the X-tile program, patients were divided into 3 risk groups, which were easily discriminated on survival analyses for OS.ConclusionWe have successfully constructed an effective nomogram to predict survival outcomes for young female patients with curatively resected BC, which may provide individual survival prediction to benefit prognosis evaluation and individualized therapy.

Correlation between Age and Prognostic Factors in Thai Breast Cancer Women: A Single Institute Analysis

Background: Breast cancer is the most common cancer in females, especially for those in their middle age between 40 to 60 years. There are prognostic factors of breast cancer such as an intrinsic subtype called triple-negative breast cancer (TNBC), HER2 overexpression, poorly differentiated, large tumor size, axillary lymph node status, and staging. Age at diagnosis is usually associated with aggressive cancer and poorer outcomes. Objective: To explore the age and prognostic factors for breast cancer in Thailand. Materials and Methods: The data were collected from pathological data collection and medical records of Buddhasothorn Hospital, Chachoengsao, Thailand, between 2015 and 2018. All data were collected for studying the relationship between age at diagnosis and prognostic factors. Results: Three hundred three cases were collected. It was found that the age between 35 to 69 years had breast cancer the most (83.83%). The intrinsic subtypes found were Hormonal receptor-positive (HR+) 67.33%, TNBC 22.11%, and HER2 overexpression 10.56%. Age under 35 years had a risk of poor prognostic factors such as poorly differentiated (OR 1.528, 95% CI 0.306 to 7.627, p=0.605), large tumor size greater than 5 cm (OR 2.145, 95% CI 0.560 to 8.221, p=0.266), and axillary lymph node metastasis (OR 1.409, 95% CI 0.345 to 5.762, p=0.633). Age of 70 years and over had more favorable prognostic factors such as well-differentiated (OR 1.691, 95% CI 0.645 to 4.436, p=0.286), no axillary lymph node metastasis (OR 1.734, 95% CI 0.886 to 3.393, p=0.108), and the HR+ subtype (OR 2.158, 95% CI 0.954 to 4.882, p=0.065). Nonetheless, the present study data did show statistical significance. Conclusion: The evidence of breast cancer in Thailand found that the different age ranges affected the prognostic factors differently. Specifically, young age breast cancer had a higher risk of poor prognostic factors, whereas the elderly breast cancer was associated with more favorable prognostic factors. However, a larger number of patient data to the confirm relationship between age and prognostic factors is required. Keywords: Breast cancer; Age-related; Prognostic factors

Differences in clinicopathological characteristics, treatment, and survival outcomes between older and younger breast cancer patients

In developing countries, breast cancer is diagnosed at a much younger age. In this study we investigate the dichotomies between older and young breast cancer patients in our region. The study involved two cohorts; older patients (≥ 65 years, n = 553) and younger ones (≤ 40 years, n = 417). Statistical models were used to investigate the associations between age groups, clinical characteristics and treatment outcomes. Compared to younger patients, older patients were more likely to present with advanced-stage disease (20.6% vs. 15.1%, p = .028). However, among those with non-metastatic disease, younger patients tended to have more aggressive pathological features, including positive axillary lymph nodes (73.2% vs. 55.6%, p < .001), T-3/4 (28.2% vs. 13.8%, p < .001) and HER2-positive disease (29.3% vs. 16.3%, p < .001). The 5-year overall survival (OS) rate was significantly better for the younger (72.1%) compared to the older (67.6%), p = .035. However, no significant difference was observed in disease-free survival (DFS) between the two groups.In conclusion, younger patients with breast cancer present with worse clinical and pathological features, albeit a better OS rate. The difference in DFS between the two groups was not insignificant, suggesting that older women were more likely to die from non-cancer related causes.

Abstract 790: A Utah Population Data Base Study of young women's breast cancer outcomes by parity status

Abstract Importance: A diagnosis of breast cancer after childbirth is reported to increase risk for metastasis and death in patients ≤45 years of age. Data to discern if a postpartum diagnosis is an independent risk factor for poor outcomes remain limited. Objective: Determine associations between time since last pregnancy and time to metastasis and breast cancer-specific death using cases available from the Utah Population Data Base (UPDB). Secondary objectives are time to metastasis and breast cancer specific-death delineated by tumor stage and ER status. Study Design: This is a population-based study of 2,977 women with stage I, II, or III breast cancer (BC) diagnosed at ≤ 45 years of age from 1996 to 2017. The study population was identified from the UPDB, a statewide dynamic database of linked data received from the Utah SEER Cancer Registry, birth certificates, death certificates, and medical records. Clinical prognostic factors include patient age at diagnosis, year of diagnosis, tumor size, stage, and estrogen receptor (ER) status. The primary exposures are no prior childbirth or time between the most recent childbirth and a breast cancer diagnosis, and primary outcomes are distant metastasis-free survival and breast cancer specific death. Results: Among the 2,977 predominantly white women from the state of Utah, USA, the reproductive histories of the breast cancer patients were grouped as nulliparous (n = 867), and parous: diagnosed 0-5 years (n = 614), &amp;gt;5-10 years (n = 615) and &amp;gt;10 years (n = 881) since last childbirth. We find a breast cancer diagnosis within 5 years of childbirth is associated with elevated risk for metastasis after controlling for diagnosis year, diagnosis age, tumor stage, and ER status [HR (95% CI) =1.64 (1.16, 2.32)], particularly in Stage I/II disease [HR (95% CI) =1.89 (1.24, 2.87)]. The 0-5 year group also had elevated risk of breast cancer-specific death [HR (95% CI) =1.57 (1.07, 2.32)]. While ER-negative tumors were enriched in women diagnosed 0-5 years postpartum, this enrichment could be attributed largely to the younger age of this reproductive group. Further, postpartum breast cancer patients diagnosed with ER-positive disease within 5 years of a completed pregnancy had significantly worse distant metastasis-free survival than nulliparous patients with ER-negative disease. Conclusions: In this population level study from the state of Utah, a diagnosis of breast cancer within 5 years postpartum is a risk factor for metastasis and breast cancer-specific death that is independent of known clinical parameters, including ER status. The increased risk for poor outcomes is highest in stage I/II diagnoses. Relevance: For women with breast cancers classically considered as having good prognostic tumor features, i.e. stage I or II and ER-positive, a postpartum diagnosis is a dominant demographic feature of increased risk for metastasis and death. Citation Format: Pepper Schedin, Sonali Jindal, Solange Bassale, Zhenzhen Zhang, Alison Fraser, Emily Guinto, Virginia F. Borges, Motomi Mori, Ken R. Smith. A Utah Population Data Base Study of young women's breast cancer outcomes by parity status [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 790.

Abstract 2695: Identification of an age-related breast cancer gene expression signature with strong prognostic value

Abstract Background and Objective: Breast cancer (BC) diagnosed at ages &amp;lt;40 years is known to present more aggressive tumor phenotypes and poorer clinical outcome compared to older BC patients. To gain a better understanding of the possible age-related expression difference in BC promoting genes, we aimed to identify transcriptional alterations supporting cancer progression in BC of the young. Methods: We studied mRNA gene expression data from METABRIC discovery (n=997), and validation cohort (n=995), and explored the transcriptional patterns associated with BC of the young. We investigated differentially expressed genes (DEGs) between primary BC for patients below and above 40 years at time of diagnosis and explored gene sets (by Gene Set Enrichment Analysis) enriched in BC of the young. Protein-protein interaction (PPI) networks were explored by the STRING database and visualized in Cytoscape software. Hub genes were identified by MCODE and CytoHubba plugins. Results: Among genes differentially expressed between BC of the young and older, 91 DEGs were commonly (for the two cohorts) upregulated and 99 commonly downregulated in the young (Fold change ≥1.5/≤ -1.5). Oncogenic- and proliferation associated signatures were enriched in the young BC, including signatures reflecting KRAS, MTOR and MYC. Proliferation and cell cycle processes were the dominating enriched gene ontology categories (FDR &amp;lt;10%). Six hub genes presenting highest PPI network connectivity were identified, described to be associated with the cell cycle and cell proliferation. A signature score was made by summarizing the hub genes expression values. High signature score was significantly associated with high tumor size, high histologic grade, lymph node metastasis, ER negativity, basal-like, and HER2 enriched subtypes (P &amp;lt;0.001). The signature score showed strong correlation with the proliferation signatures OncotypeDx and PCNA (ρ=0.90-0.96, P &amp;lt;0.001). Our signature score associated with reduced cancer specific survival (P &amp;lt;0.001), also when adjusted for tumor size, histologic grade, and lymph node status in multivariate analyses in both cohorts (HR: 1.074-1.081, 95% CI: 1.046-1.109, P ≤0.003). The signature score maintained independent, significant association with survival when adjusting for the traditional clinico-pathologic variables in OncotypeDx-low tumors in discovery (HR: 1.077, 95% CI: 1.034-1.122) and validation cohort (HR: 1.154, 95% CI: 1.065-1.251), both P &amp;lt;0.001. Conclusion: By genome-wide gene expression analyses, the current study provides new insights into age-related gene expression alterations in breast cancer. We demonstrate enrichment of oncogenic signaling and evidence of higher tumor cell proliferation in young BC patients, and identify a gene expression signature reflecting tumor proliferation, aggressive tumor features and reduced survival, also in subsets of low OncotypeDx score. Citation Format: Lise Martine Ingebriktsen, Lars Andreas Akslen, Elisabeth Wik. Identification of an age-related breast cancer gene expression signature with strong prognostic value [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 2695.

Abstract 879: Validation of the Nigerian Breast Cancer Study model for predicting individual breast cancer risk in Cameroon and Uganda

Abstract Background: Women of African ancestry across the diaspora have low risk of developing breast cancer compared to women of European ancestry. However, they suffer the highest mortality rates because of the disproportionate burden of young onset aggressive hormone receptor negative breast cancer. To implement strategies for early detection and prevention, it is critically important to develop better risk assessment tools. The Nigerian Breast Cancer Study (NBCS) model is a new risk assessment tool developed for the individual estimation of absolute risk of invasive breast cancer in Nigeria. Its applicability outside of Nigeria remains uncertain as it has not been validated in other Sub-Sahara African (SSA) populations. Methods: We conducted a case-control study among women with breast cancer and controls ascertained in Cameroon and Uganda from 2011 to 2016. Structured questionnaire interviews were performed to collect demographic and reproductive characteristics. The NBCS model, the Gail model for white population, the Gail model for Black population (CARE), and the Black Women's Health Study (BWHS) model were applied to the Cameroon and Uganda samples separately. Local incidence rates were incorporated into the NBCS model for the Uganda analysis. Receiver-Operating Characteristic (ROC) analyses were performed and the area under ROC curve was used to indicate discriminating capacity. Results: The cohort included 549 cases (mean age 47 ± 11.94) and 509 Controls (mean age 46 ± 11.68). Compared to the other three models, the NBCS model performed best in both countries. The discriminating accuracy of the NBCS model in Cameroon (age-adjusted C-index = 0.599, 95% CI 0.540-0.658) was significantly better than in Uganda (age-adjusted C-index = 0.511, 95% CI, 0.437-0.585). In Cameroon, the BWHS model had slightly lower distinguishing ability (age-adjusted C-index = 0.588, 95% CI, 0.528-0.647) and gave lower risk estimates in cases than the NBCS model. The Gail and CARE models performed poorly in both countries. Conclusions: These findings demonstrate the potential clinical utility of the NBCS model for risk assessment in Cameroon. All currently available models performed poorly in Uganda, which suggests that the NBCS model may need further calibration before use in other regions of Africa. Differences in risk profiles across the African diaspora underscores the need for larger studies and may require development of country or region-specific risk assessment tools for breast cancer. Citation Format: Kevin Ashi, Paul Ndom, Antony Gakwaya, Timothy Makumbi, Olufunmilayo I. Olopade, Dezheng Huo. Validation of the Nigerian Breast Cancer Study model for predicting individual breast cancer risk in Cameroon and Uganda [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 879.

Abstract 813: Clinical significance of pathogenic variants in germline BRCA1/2 wild type patients at risk for hereditary breast cancer

Abstract Objectives: Approximately, 5-10% of breast cancer (BC) are related to inherited germline mutations. Homologous recombination repair (HRR) of DNA is the most important theory in hereditary cancer, in which BRCA1/2 are the most recognized and tested genes. Genetic testing for hereditary BC has changed significantly. Increasing evidence suggests parallel multigene testing of HRR gene. Methods: NGS-based germline multigene-panel testing of 105 HRR gene was performed on 159 high risk BC patients with at least one of the following risk factors: triple negative BC, early onset (≤45y), family history of BC and bilateral BC. Capture-base targeted sequencing was performed on white blood cells using a panel consisting of 105 genes related to homologous recombination repair of DNA. Results: Among the 159 patients of median age 40, All the patients had early stage infiltrating ductal carcinoma. 12 patients (7.55%) had pathogenic BRCA1/2 mutation. We investigated the prevalence of 21 pathogenic germline pathogenic mutations beyond BRCA1/2 from 21 patients spanning 13 HRR genes, resulting in a prevalence rate of 13.21% for pathogenic germline mutations in high risk germline BRCA1/2 WT BC patients. PALB2 is the most common gene with pathogenic mutation (n=5). In these 21 patients, 18 (85.71%) were diagnosed with BC before the age of 45, within 7 patients (33.33%) even younger than 35 years old. 7 of them (33.33%) had bilateral BC; one had triple negative BC (4.76%) and 5 patient (23.81%) had a family history of BC. Nearly half of the patients (n=9) presented at least 2 of the risk factors. Conclusions: Our study confirms the clinical significance of testing non-BRCA genes, and suggests multigene panel testing for patients at risk for hereditary BC as a routine in patients with those risk factors, especially young and bilateral BC patients even without family history of BC. Citation Format: Xiaying Kuang, Nan Shao, Ying Lin. Clinical significance of pathogenic variants in germline BRCA1/2 wild type patients at risk for hereditary breast cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 813.

Young breast cancer and the influence of ethnicity in Sandakan: A 3-year retrospective cross-sectional study.

Breast cancer (BC) is the most common cancer in Malaysia, with incidence increasing with age. There have been demonstrated differences in age of presentation and tumour biology when comparing ethnicities. Twenty percent of Caucasian women present before 50 years old, but almost 50% of Southeast Asian (SEA) women present before 50. However, BC in Indigenous sub-groups has not yet been studied. Sandakan is a city in Sabah with a large Indigenous population. Current nationwide screening guidelines are based on the U.S. Preventive Task Force 2009 Guidelines, which may not represent our population. We aim to examine the age of incidence for our local population, for local screening recommendations. Retrospective cross-sectional study, including all consecutive cases of epithelial invasive tumours, from January 2016 to December 2018. Other histological types were excluded. Univariate and multivariate analyses were performed. A total of 115 breast tumours were identified. Ten tumours were excluded (five ductal carcinoma in situ, four phyllodes, and one sarcoma), leaving a study population of 105 patients. Median age of presentation was 53 years (min 30; max 97). A total of 41.9% presented before the age of 50. Patients of Indigenous ethnic origins were 11years younger at presentation than non-Indigenous women. Tumour grade was more likely to be higher among Indigenous women. Median age of presentation of BC in Sandakan matches regional data; however, patients of Indigenous ethnic groups present even earlier. Screening guidelines should consider the growing evidence of young BC in SEA.

Predictive Role of Leptin Receptor (Ob-R) Overexpression in Patients with Early Breast Cancer Receiving Neoadjuvant Systemic Treatment.

Simple SummaryObesity and overweight, considered the pandemic disease in the 21st century, is highly related to breast cancer. Leptin receptor (Ob-R) and its ligand leptin display an important role in driving this connection. Nowadays, translational cancer research is mainly focused on the identification of new biomarkers able to discriminate those patients deriving greater efficacy from a given therapy. In this regard, our study examines the role of Ob-R, namely, the correlation between Ob-R and pathological complete Response (pCR) in early breast cancer patients receiving neoadjuvant systemic therapy. Here, we decoded the correlation of Ob-R with certain clinical features such as breast cancer subtype, age, body mass index (BMI), menopausal status, and mammogram breast density. The study provides further support for the potential value of Ob-R for the first time as a possible role for predicting pCR. Moreover, we would like to highlight the importance of Ob-R as independent predictive factors for pCR in breast cancer patients.The primary aim of this retrospective study was to investigate the correlation between the immunohistochemical expression of Ob-R (leptin receptor) with pCR (pathological complete response) in early breast cancer patients receiving neoadjuvant systemic treatment (NST). A total of 100 women with breast cancer receiving NST (2017–2020) followed by surgical resection were retrospectively obtained. Demographic parameters and clinicopathological factors (e.g., treatment modalities, immunohistochemistry (IHC), and cancer subtype) were obtained from the patient’s clinical records. In the analyzed breast cancer cohort, high expression of Ob-R was found in 52% of tumors and there was a significantly higher incidence in the HER2+ and TNBC subgroups. Overall, a significantly greater percentage of patients with Ob-R positive tumors achieved pCR compared with Ob-R negative patients (57.7% vs. 27.1%; p = 0.002). This result was observed in most breast cancer subtypes. In patients with HER2+ breast cancer, there was no difference in Ob-R expression in relation to the HR status. Ob-R cell positivity was significantly higher in younger breast cancer patients (p = 0.008), those who were premenopausal (p = 0.011), and in those with a BMI > 25 kg/m2 (p = 0.019). A significantly greater percentage of early breast cancer patients with Ob-R positive tumors achieved pCR compared with Ob-R negative patients. Furthermore, breast cancer patients with positive Ob-R expression were significantly younger than those with negative Ob-R expression. This association was not explained by differences in BMI between young and old patients.

Association of cognitive impairment and breast cancer survivorship on quality of life in younger breast cancer survivors

PurposeYounger breast cancer survivors (BCS) often report cognitive impairment and poor quality of life (QoL), which could be interrelated. The purpose of this study was to examine the association of cognitive impairment and breast cancer status (BCS versus healthy control (HC)), with QoL, which included psychological (depressive symptoms, well-being, perceived stress, and personal growth) and physical well-being (physical functioning and fatigue).MethodsFour hundred ninety-eight BCS (≤45 years at diagnosis) who were 3 to 8 years post-chemotherapy treatment and 394 HC completed subjective questionnaires and a one-time neuropsychological assessment, including tests of attention, memory, processing speed, and verbal fluency. For each test, cognitive impairment was defined as scoring 1.5 and 2.0 standard deviations below the mean of the HC group. Separate linear regression models for each outcome were ran controlling for known covariates.ResultsBCS reported significantly more memory problems than HC (p < 0.0001), with up to 23% having significant impairment. Cognitive performance did not differ significantly between BCS and HCs. BCS vs. HCs had greater depression and fatigue, yet more personal growth. Objective and subjective cognitive impairment were significantly related to greater depressive symptoms and perceived stress and lower well-being and physical functioning; whereas, objective impairment was related to less personal growth and subjective impairment was related to greater fatigue.ConclusionsYounger BCS report significant cognitive impairment years after treatment which may relate to greater decrements in QoL.Implications to Cancer SurvivorsAssessment and interventions to address cognitive concerns may also influence QoL outcomes in younger BCS.

The feasibility of same day pegfilgrastim-cbqv administration in breast cancer patients receiving myelosuppressive chemotherapy regimens at a northern Virginia cancer center.

e18687 Background: The long-acting injectable G-CSF, pegfilgrastim and its biosimilars have historically been given to patients 24 hours following the administration of myelosuppressive chemotherapy for either primary or secondary prophylaxis of febrile neutropenia (FN). Previous literature has indicated that pegfilgrastim administration prior to 24 hours post chemotherapy, may result in a deepened and prolonged neutropenia due to the increase in circulating granulocytes exposed to chemotherapy. With the onset of the COVID-19 pandemic and to reduce potential SAR-CoV-2 exposure to cancer patients on therapy, we implemented same day administration of injectable pegfilgrastim-cbqv among select breast cancer patients receiving myelosuppressive chemotherapy regimens from March 2020 – February 2021. Methods: Utilizing retrospective EHR chart reviews, 55 patients among 4 medical oncologists in our breast cancer group were identified as meeting the criteria of same day pegfilgrastim-cbqv administration. Inclusion was based on completion of at least 2 consecutive cycles of same day pegfilgrastim-cbqv 6 mg subcutaneous injection for primary or secondary prophylaxis. The selected patient charts were reviewed for the incidence and severity of FN. Among the patients who had documented FN, further subgroup analyses were done regarding baseline characteristics, timing of neutropenia, regimens, regimen sequence, and reported ADRs associated with pegfilgrastim-cbqv. Results: 9 (16.4%) of the 55 patients experienced FN (Grades 3-4) and 6 (10.9%) patients were hospitalized. There were no Grade 5 events and none had therapy discontinued due to FN. 8 (88.9%) of the patients experienced FN between cycles 1 and 2. Of note, there were no cases of COVID-19 among the 9 patients who had an episode of FN. 52 (94.5%) of the 55 patients received treatment with curative intent and 3 (5.5%) had metastatic disease on a subsequent line of therapy. The median age was 49.1 years (range 29-71) and patients were 56.4% Caucasian, 18.1% Black or African American, 12.7% Asian, and 12.7% Hispanic/Latina. Conclusions: Based on the retrospective data analysis, same day pegfilgrastim-cbqv appears to be a safe and effective option in the primary and secondary prophylaxis of FN with myelosuppressive standard of care chemotherapy used in breast cancer treatment. Though our review was limited by a relatively small sample size and confined to younger (49.1 median age) breast cancer patients, this opens the door to further re-evaluation of same day pegfilgrastim-cbqv administration in other patient populations. In a post pandemic treatment world, this slight change in practice has the potential to reduce patient financial toxicity associated with multiple medical visits, provide an alternative to on-body injector formulations, and ensure treatment adherence.

Differences in clinicopathological characteristics, treatment, and survival outcomes between older and younger breast cancer patients: A regional perspective.

e18604 Background: In developing countries, breast cancer treatment outcomes may be uniquely affected by the tendency of breast cancer patients to develop the disease at a much younger age than the worldwide average. Contrarily, older patients tend to present with multiple comorbidities that complicate their outcomes and influence their treatment options and decisions. This study will be the first to investigate the dichotomies between older and young breast cancer patients in our region. Methods: The study was based on data collected from the cancer registry of our institution for breast cancer patients 65 years or older (n = 553), and patients 40 years or younger (n = 417) at time of diagnosis. Statistical models were used to investigate the associations between age groups, clinical characteristics and treatment outcomes. Results: A total of 970 patients were included in the final analysis. Compared to younger patients, older ones were more frequently diagnosed with distal metastasis; 20.6% compared to 15.1%, p =0.028. However, among patients with non-metastatic disease, younger ones tended to have more aggressive pathological features, including positive axillary lymph nodes (73.2% vs. 55.6%, p&lt; 0.001), T-3/4 (28.2% vs. 13.8%, p&lt; 0.001) and HER2-positive disease (29.3% vs. 16.3%, p&lt; 0.001). A higher percentage of patients from the young cohort underwent surgery (85.4%) when compared to the older group (74.9%), p&lt; 0.001. More patients in the older group had mastectomy than did younger patients (67.5% versus 40.2%, p&lt; 0.001), while breast conserving surgery (BCS) was performed on almost a third in each cohort, p= 0.245. Skin-sparing, with or without, nipple-sparing mastectomies (SSMs) along with breast reconstruction surgery were more frequently performed on younger patients than they were on the older patients. After a median follow-up of 59 months for the younger patients and 45 months for the older ones, the 5-year OS rate of the older patients was 67.6% compared to 72.1% for the younger patients, p= 0.035. However, the 5-year DFS rates of the two cohorts were not statistically different at 63.9% for the older group and 60.7% for the young patients, p= 0.31. The survival of patients with non-metastatic disease was also compared among both groups; the 5-year OS among the younger patients was significantly higher (83.6% compared to 78.8% among the older patients, p= 0.046). Survival was better among the younger patients across many clinical and pathological characteristics. Conclusions: Younger patients with breast cancer present with worse clinical and pathological features, albeit a better OS rate. The difference in DFS between the two groups was insignificant, suggesting that older women were more likely to die from non-cancer related causes.

Testing for clonal hematopoiesis of indeterminate potential in breast cancer survivors.

e24108 Background: Clonal hematopoiesis of Indeterminate Potential (CHIP) is associated with adverse clinical outcomes including increased risk of hematologic malignancies and heart disease. Limited data suggest an increased prevalence of CHIP in patients treated for solid tumors, particularly after exposure to radiation and chemotherapy. CHIP testing may inform risk-reduction strategies for cancer survivors. Little is known about patient knowledge, attitudes, and preferences regarding CHIP testing. Methods: We surveyed survivors without history of recurrence participating in an ongoing prospective cohort study of young women with breast cancer (BC). The survey was sent by email and included an introduction to CHIP including risk factors and clinical associations. Respondents then reviewed a vignette and were asked about CHIP testing preferences (definitely/probably test vs. definitely/probably not test) considering sequentially: 1) population-based 10-year risk of BC recurrence, hematological malignancy and heart disease; 2) estimated increase in these risks with CHIP; 3) current CHIP management; 4) a dedicated CHIP clinic; and 5) a theoretical CHIP treatment. Changes in preferences from the prior scenario were evaluated with the McNemar's test using a type I error rate of 5%. Results: 528/642 (82.2%) eligible women responded to the survey, at a median age of 46 (range: 31-54) years (median time from diagnosis: 108 months (range: 60-168)), and 88% were white. Most had stage 1/2 BC (78.8%) and had received chemotherapy (73.1%) and/or radiation (61.9%). 93.6% had never heard of CHIP prior to survey. After initial patient vignette presentation, most women (87.1%,) recommended CHIP testing if offered. Preferences for testing decreased (p&lt;0.05) when considering population-based risks, with 11.1% shifting their preference from CHIP testing to not testing. After considering increased risks associated with CHIP, interest in testing increased (p&lt;0.05), with 10.1% shifting their preference to testing. Interest significantly (p&lt;0.05) increased with the possibility of managing CHIP through a clinic or a hypothetical CHIP treatment, with 7.2% and 14.1% switching their preferences towards testing, respectively. Finally, 75.8% responded that they themselves, after learning about CHIP and reviewing the vignette, would want to have CHIP testing; 28.2% reported that learning about CHIP and the associated risks caused them at least moderate anxiety. Conclusion: Few young BC survivors were aware of CHIP yet most indicated an interest in testing after learning about it. Testing preferences were influenced by risks presented and potential management strategies. Findings highlight the importance of effective risk communication and the need for adequate psychosocial support when considering testing for CHIP and other potential clinical biomarkers predictive of cancer and other medical risks in cancer survivors.

Retrospective analysis of HER2-low in young breast cancer patients.

e12515 Background: Traditionally, breast cancer (BC) is considered human epidermal growth factor receptor-2 (HER2) positive based on HER2 overexpression or amplification (HER2 3+ or ISH positive HER2 2+). However, an emerging subgroup of HER2 negative (HER2 1+ or 2+ and ISH negative) known as HER2-Low is associated with poor prognosis than HER2-normal (HER2 0). Currently, there is an increased interest in developing new drugs targeting HER2-Low BC to improve survival. The fact that BC in young constitutes a significant minority outside the western world but is underrepresented in clinical trials, it is worth conducting a dedicated study of HER2-low in this population to determine whether it affects their outcome. Methods: Confirmed HER2 negative BC patients aged ≤40 diagnosed in 2012-2017 were retrospectively reviewed in two centers in Alexandria, Egypt. Patients were classified as HER2-low (1+, 2+) and HER2-normal. The clinicopathological characteristics and survival outcome were determined and compared. Results: There were five hundred HER2 negative BC patients; 82% were hormone receptor-positive (HR+) vs.18% triple-negative (TNBC). Among the HER2 negative, only 31% were HER2-Low (n = 155), of which 20% was HER2-Low 1+ while 11% was HER2-Low 2+. In comparison, HER2-Low was significantly more HR+ than HER2-normal (89% vs. 79% respectively, p = 0.009). Other tumor characteristics (T-size, nodal status, Ki-67, lymphovascular invasion - LVI, extracapsular extension - ECE) were similar in HER2-Low and HER2-normal. So were the disease-free survival (DFS) and overall survival (OS). Nevertheless, sub-grouping HER2-Low into 1+ and 2+ showed significant differences in tumor characteristics between HER2-normal, HER2-Low 1+, and HER2-Low 2+, in nodal status, tumor stage, ECE, and HR status. Moreover, DFS was significantly lower in HER2-Low 2+ (63.5%) compared to HER2-normal (70%) and HER2-Low 1+ (75%); p = 0.039. Also, the OS was also significantly lower in HER2-Low 2+ compared to HER2-normal, 90% vs 96% respectively, p = 0.023. Conclusions: Our results suggest no significant difference in DFS and OS between HER2-Low and HER2-normal in young BC patients. However, subdividing HER-low into HER2-low 1+ and HER2-Low 2+ better discriminates this group; HER2-Low 2+ had significantly poor DFS and OS and this should be considered in the clinical trials.

136P The incidence and prognostic impact of obesity in young Egyptian breast cancer patients

The breast cancer (BC) incidence of young women in Africa and the Middle East is higher than that of the western population. Growing evidence shows a global increase in obesity incidence. Both obesity and young age are associated with poor survival in BC. Thus, it is relevant to address this question in this population. We retrospectively reviewed 720 female BC patients ≤40 years who had the weight and height data in two centers in Alexandria – Egypt. The body mass index (BMI) was categorized according to WHO groups into underweight – UW (BMI 18.5 kg/m2), normal weight - NW (BMI ≥18.5 to < 25kg/m2), overweight – OW (BMI ≥25 to < 30kg/m2), obese – Ob (BMI >30 kg/m2). We determined the obesity incidence, clinicopathological features, and the impact of obesity on survival by Kaplan Meir and Cox regression. The median follow-up was 44 months (1 - 143). The BMI distribution was UW - 1.7% (12), NW - 11.1% (80), OW - 26.8% (193), Ob - 60.4% (435); more than 85% were Ob/OW. The median age in UW/NW, OW, and Ob was 34, 35, and 37 years, respectively. Ob patients were significantly older, p < 0.001. The mean tumor size was 3.4cm in UW/NW, 3.7cm – OW, and 3.7cm - Ob. The Ob had a significantly higher incidence of high nodal involvement (44%; p − 0.023), and significantly estrogen/progesterone negative (21.2%; p − 0.016). Ki-67 was higher in Ob (57.4%) and OW (74%) than UW/NW (50%); p – 0.222. The distant relapse rates were insignificantly higher in Ob - 25.7% and OW - 25.5% than UW/NW - 20.2%; p – 0.352. There were no significant differences in the mean disease-free survival (CI: 81 – 96; p-0.692) and the overall survival (CI:120 – 124; p-0.186). In the multivariate analysis and cox regression, obesity did not impact survival. There is an alarmingly high incidence of Ob/OW among young Egyptian BC patients. Our results confirm that Ob patients have more aggressive features than UW/NW. Nevertheless, our results suggest that, despite the poor prognostic factors characteristics, higher BMI did not worsen the survivals.

Loco-regional recurrence trend and prognosis in young women with breast cancer according to molecular subtypes: analysis of 1099 cases

BackgroundThe number of young patients diagnosed with breast cancer is on the rise. We studied the rate trend of local recurrence (LR) and regional recurrence (RR) in young breast cancer (YBC) patients and outcomes among these patients based on molecular subtypes.MethodsA retrospective cohort study was conducted based on data from Tianjin Medical University Cancer Institute and Hospital for patients ≤ 35 years of age with pathologically confirmed primary invasive breast cancer surgically treated between 2006 and 2014. Patients were categorized according to molecular subtypes on the basis of hormone receptor (HR) and human epidermal growth factor receptor 2 (HER2) status. The 5-year rates for LR, RR, and distant metastases (DM) were estimated by Kaplan-Meir statistics. Nelson-Aalen cumulative-hazard plots were used to describe local recurrence- and distant metastasis-free intervals.ResultsWe identified 25,284 patients with a median follow-up of 82 months, of whom 1099 (4.3%) were YBC patients ≤ 35 years of age. The overall 5-year LR, RR, and DM rates in YBC patients were 6.7%, 5.1%, and 16.6%, respectively. The LR and RR rates demonstrated a decreasing trend over time (P = 0.028 and P = 0.015, respectively). We found that early-stage breast cancer and less lymph node metastases increased over time (P = 0.004 and P = 0.007, respectively). Patients with HR−/HER2+ status had a significantly higher LR (HR 20.4; 95% CI, 11.8–35.4) and DM (HR 37.2; 95% CI, 24.6–56.3) at 10 years. Breast-conserving surgery (BCS) or mastectomy did not influence rates of LR and RR. In the overall population, the 5-year survival of YBC patients exceeded 90%.ConclusionsThe rates of LR and RR with YBC patients demonstrated a downward trend and the proportion of early-stage breast cancer increased between 2006 and 2014. We report the highest LR rates in this young population were associated with HR−/HER2+ tumors.

Sole adjuvant intraoperative breast radiotherapy in Taiwan: a single-center experience

IntroductionIntraoperative radiotherapy (IORT) is more convenient than standard whole breast external beam radiotherapy (EBRT) as a sole adjuvant radiotherapy for breast cancer. The impact of age on breast cancer course and treatment strategy is still under investigation, and the peak age for breast cancer in Taiwan is much younger than that in Western countries. We aimed to review the oncological outcomes of sole IORT compared with standard EBRT in a country with younger breast cancer patients.Patients and methodsWe reviewed patients with invasive breast cancer who received breast-conserving surgery (BCS) from September 2014 to December 2016. The clinicopathologic characteristics and oncological outcomes of eligible patients who received EBRT or IORT as sole adjuvant radiotherapy after BCS were collected and reviewed.ResultsA total of 170 patients were enrolled with a mean follow-up time of 3.53 ± 0.82 years. The risk of locoregional recurrence was 2.44% for EBRT versus 10.64% for IORT (p = 0.024). IORT was a significant risk factor of locoregional recurrence (p = 0.005). The hazard ratios (HRs) for locoregional recurrence in the IORT group compared with the EBRT group were significantly higher in non-suitable risk group patients (HR = 7.02, p = 0.009) and in patients under 50 years old (HR = 10.42, p = 0.011).ConclusionsLocoregional recurrence was significantly higher in patients who received IORT than in those who underwent EBRT. IORT should not be used alone in patients under 50 years old who do not belong to a suitable group.

New germline mutations in BRCA1, ATM, MUTYH, and RAD51D genes in Tuvans early-onset breast cancer patients.

In Russia, more than 50,000women are diagnosed with breast cancer (BC) every year. Russia is a multinational country- about 200ethnic groups live on its territory. Khakass, Buryats, Tuvans and other ethnic groups show higher rate of increase in BC incidence and a younger age of first diagnosed BC compared to Caucasian ethnicities. We focused on Tuvan ethnic group to find specific genetic aberrations associated with BC. There are no BC prevention models as well as standards for the treatment of inherited BC in Tuvans. In this context, the search for genetic markers of early cancer detection and the development of criteria for therapy response are relevant. To identify hereditary mutations in BC-associated genes in Tuvan women. 24patients with early-onset BC (range, 25to 46years) were enrolled in the study. Genomic DNA isolated from blood samples was used to prepare libraries using a capture-based target enrichment kit covering 27genes (ATM, APC, BARD1, BRCA1, BRCA2, BRIP1, CDH1, CHEK2, EPCAM, FAM175A, MLH1, MRE11A, MSH2, MSH6, MUTYH, NBN, PALB2, PIK3CA, PMS2, PMS2CL, PTEN, RAD50, RAD51C, RAD51D, STK11, TP53and XRCC2). Next-generation sequencing was performed using the Illumina NextSeq500System. In our study, one pathogenic mutation was detected in BRCA1 (rs80357868) gene (prevalence of 4%, 1/24). We identified the truncating 3875_3878delGTCT mutation of BRCA1gene in Tuvans BC patient aged 34years. We also detected three mutations that were probably damaging by PolyPhen2and/or deleterious by SIFT in ATM (rs781023264), MUTYH (rs199840380) and RAD51D (rs145309168) genes. To the best of our knowledge, this is the first report that describes the highly pathogenic variant in the BRCA1gene (rs80357868) and possibly damaging (PolyPhen2) germline variants in the ATM (rs781023264), MUTYH (rs199840380) and RAD51D (rs145309168) genes in young Tuvans BC patient.