An audit of breast cancer in patients 40 years and younger in two Johannesburg academic hospitals.

In 2019, 13,050 young women were diagnosed with pre-invasive or invasive breast cancer in the USA and 1070 women died of their disease. Young women are underrepresented in clinical trials, and treatment for these women less than 40 years old is extrapolated from studies of older women. Young women face unique challenges such as decreased fertility, psychosocial issues and an extended survivorship period that impacts quality of life. Herein, we review breast cancer treatment options in the young patient (women <40 years old). We explore the biologic differences between breast cancer in young versus older patients, review surgical and systemic therapy options and highlight special considerations that are unique in these young patients.

Background Breast cancer is relatively rare in women younger than 35 years of age, accounting for 2–4% of the total number of breast cancer cases diagnosed each year in western countries and the USA 1–3. However, the proportion of young age-onset breast cancer was much higher in the Asian population 3–6. Breast cancer at a young age has been reported to have a more aggressive biological behavior and to be associated with worse prognosis compared with the disease in older patients 5,7–17. Higher incidence of recurrence and risk of death were detected in younger patients, even when more aggressive therapies were administered 10–14. Neoadjuvant chemotherapy (NCT) has been considered the standard treatment for locally advanced breast cancer patients. In human epidermal growth factor receptor 2 (HER2)-positive and triple-negative tumors, achievement of a pathological complete response (pCR) after NCT was associated with better survival outcomes 18. In recent studies, young breast cancer patients were reported to obtain higher pCR rates compared with older counterparts 19,20. However, it remains unclear whether pCR is a predictor for better prognosis in young breast cancer patients. In this study, we aimed to investigate chemotherapy response and its relation with prognosis in young breast cancer patients (<35 years old) who were treated with NCT. Patients and methods Patients From January 2003 to December 2013, patients with operable or locally advanced breast cancer who were treated with NCT at the Cancer Hospital, Chinese Academy of Medical Sciences, and Peking Union Medical College were reviewed systemically. The inclusion criteria for the study were as follows: (i) 35 years or younger or 60 years or older; (ii) diagnosis of invasive carcinoma confirmed by core needle biopsy before NCT and the lymph node status was evaluated by fine needle aspiration of palpable lymph node if applicable; (iii) immunohistochemical examination for estrogen receptor (ER), progesterone receptor (PgR), and HER2 status using tumor specimens from core needle biopsy; (iv) newly diagnosed breast cancer patients; (v) combination of paclitaxel and carboplatin (PC) in patients with triple-negative breast cancer as NCT; for other patients, a combination of cyclophosphamide and epirubincin (CE) as NCT with postoperative paclitaxel, or epirubincin in combination with paclitaxel (ET) as NCT 21; (vi) adequate hematologic, hepatic, and renal functions. The exclusion criteria for the study were as follows: (a) stage IV disease, bilateral breast cancer, male breast cancer, and patients complicated with other malignancies; (b) patients who did not have complete clinical information or immunohistochemistry; (c) patients who were lost to follow-up immediately after treatment. This study was a retrospective observational research and patients' information was collected in the hospital database. There was no direct intervention in patients' treatment or care. Therefore, a patient's consent was not required. This study was approved by the Ethics Committee of Cancer Hospital, Chinese Academy of Medical Sciences, and Peking Union Medical College. Treatment Before the initiation of NCT, bilateral breast MRI or ultrasound, chest radiography, abdominal ultrasound, or computed tomography scans were performed to determine clinical stage. All patients were staged according to the 7th TNM (tumor–node–metastasis) staging system maintained by the American Joint Committee on Cancer (AJCC). All patients received NCT with CE, or ET, or PC regimens. CE-T regimen: cyclophosphamide 600 mg/m2 intravenously, day 1, and epirubicin 80 mg/m2 intravenously, day 1, q14d×4 cycles in NCT, followed by postoperative sequential paclitaxel 175 mg/m2 intravenously, day 1, q14d×4 cycles; ET regimen: epirubincin 75 mg/m2 intravenously, day 1, and paclitaxel 175 mg/m2 intravenously, day 2, q21d×4 cycles as NCT; and two cycles of ET regimen were repeated after surgery; PC regimen: paclitaxel 175 mg/m2 intravenously, day 1, and carboplatin area under the curve=5 intravenously, day 1, q21d×6 cycles as NCT. Mastectomy or breast-conserving surgery was performed within 1 month after the completion of NCT. Adjuvant radiotherapy was prescribed at the discretion of physicians mainly on the basis of the TNM stage before NCT, followed by endocrine therapy in cases with ER-positive or PgR-positive tumors. Trastuzumab was recommended in HER2-positive patients, but not compulsory. Efficacy evaluation Clinical efficacy was estimated every two cycles by clinical, mammographic, B-ultrasound examinations, and MRI according to Response Evaluation Criteria in Solid Tumors 1.1 criteria. Pathological efficacy was assessed by pathologic report after surgery and imaging data. Efficacy evaluation indicators included pCR, clinical complete response (CR), clinical partial response (PR), overall objective response rate (ORR=CR+PR), clinical progressive disease (PD), and clinical stable disease (SD). pCR was defined as no histological evidence of malignancies or only in-situ residuals in breast tissue after surgery, and complete disappearance of lymph node metastasis. CR was defined as disappearance of all known lesions. PR was defined as at least a 30% decrease in the sum of the largest diameters of target lesions. PD was defined as at least a 20% increase in the sum of the largest diameters of target lesions or new lesions detected. SD was defined as a reduction in the largest sum diameters of tumors by no more than 30% or an increase of no more than 20%. Patients with overall objective response rate received planned treatment and sequential surgery. Patients who fulfilled the criteria for SD or PD at the initial efficacy evaluation received surgery as soon as possible and were then treated with alternative postoperative regimens. Statistical analysis All data were analyzed using SPSS medical statistical software (version 15.0; SPSS Inc., Chicago, Illinois, USA). Disease-free survival (DFS) was defined as the period from the date of receiving NCT to the date of recurrence or metastasis or last follow-up; overall survival (OS) was defined as the period from the date of receiving NCT to the date of death for any cause or last follow-up. Both OS and DFS were analyzed using the Kaplan–Meier method. Comparisons of OS or DFS between groups were performed using the log-rank test. A two-tailed P value less than 0.05 was considered statistically significant. The χ2 or Fisher's exact test was performed to compare the clinicopathological variables and pCR rates between the subgroup of younger than 35 years of age and the subgroup of older than 60 years of age. Results Patient characteristics and treatment From January 2003 to December 2013, a total of 141 breast cancer patients were enrolled in this study and 74 (52.5%) of these patients were younger than 35 years old. As shown in Table 1, younger patients presented a tendency to have a tumor size of more than 5 cm (P=0.085), to have axillary positive nodes (P=0.118), and to have lymphovascular invasion (P=0.007) compared with their older counterparts (≥60 years old). As for the treatment, younger patients were more likely to choose breast-conserving surgeries (P=0.024) and to receive adjuvant radiotherapy after surgeries (P<0.001). For the entire cohort, the median number of NCT cycles was 4 (range: 4–6 cycles). The chemotherapy regimens were changed for a total of 31 patients who had a poor response to preoperative chemotherapies (including 26 SD and five PD). Overall, 52% (16/31) of these patients were in the young group, and the other 15 patients were older than 60 years. All 96 patients with preoperative or postoperative pathological ER-positive or PgR-positive breast cancer received different postoperative adjuvant endocrine therapies. In all, 18.9% (14/74) of patients in the young group and 16.4% (11/67) of patients in the old cohort received 1 year of trastuzumab after surgery or adjuvant chemotherapy.Table 1: Patients' baseline characteristicsTreatment response All patients were evaluable for response to NCT. The rates of pCR, clinical PR (except clinical PR, but confirmed as pCR finally), clinical SD, and clinical PD were 12.8% (18/141), 65.2% (92/141), 18.4% (26/141), and 3.5% (5/141), respectively. pCR rates were similar between the young group and the old cohort (12.2 vs. 13.4%, P=0.821). The PC regimen tended to yield higher pCR rates in the young cohort, but this was not statistically significant. HER2-positive or inflammatory breast cancer patients in young group were also more likely to achieve pCR compared with their older counterparts. As shown in Table 2, there were no significant differences between the pCR rates of young and old patients across various subgroup analyses, including hormone receptor status, axillary lymph node metastasis from primary tumors, primary tumor size, HER2 expression status, and NCT regimens.Table 2: Clinical and pathological factors affecting pathological complete response ratesSurvival analysis By the last follow-up on 1 November 2015, with a median follow-up of 32 months, 38 relapse events and 11 deaths have occurred. Patients in the young group showed significantly lower 5-year DFS compared with their old counterparts (Fig. 1a, 62.2 vs. 77.8%, P=0.037). However, no significant difference in 5-year OS was observed between the young group and the old cohorts (Fig. 1b, 84.0 vs. 94.8%, P=0.212).Fig. 1: (a) Kaplan–Meier curves of disease-free survival (DFS) in the young group (N=74) and the elderly group (N=67); Kaplan–Meier curves of overall survival (OS) in the young group (N=74) and the elderly group (N=67).In the group of young patients, pCR was not a significant predictor for DFS (Fig. 2a, P=0.408), whereas significant differences were observed with respect to the ascending TNM stage at diagnosis (Fig. 2b, P=0.001). In the subset of old patients, neither pCR nor TNM stage was a prognostic factor against DFS (Fig. 2c, P=0.129 and Fig. 2d, P=0.174).Fig. 2: Disease-free survival (DFS) curves by chemotherapy response (a) and TNM stage at diagnosis (b) in young patients; DFS curves by chemotherapy response (c) and TNM stage at diagnosis (d) in old patients. pCR, pathological complete response.To further explore the difference in survival between young and old groups, we carried out a stratified analysis. As shown in Fig. 3, the 5-year DFS was lower in the young group than in the old group within the subgroup of patients who presented with inflammatory breast cancer [56.5 vs. 75.1%, hazard ratio (HR)=2.47, P=0.044], with a large primary tumor (46.7 vs. 81.4%, HR=2.93, P=0.053), with lymph node involvement (57.7 vs. 74.8%, HR=2.40, P=0.025), and with higher TNM stage at diagnosis (46.7 vs. 67.1%, HR=2.52, P=0.027). Subgroup analyses on OS were carried out across predefined subsets and no significant difference was observed (Fig. 4).Fig. 3: Forest plot of disease-free survival. Hazard ratio more than 1 indicated that old patients had better survival outcome. CI, confidence interval; ER, estrogen receptor; PgR, progesterone receptor; TNBC, triple-negative breast cancer.Fig. 4: Forest plot of overall survival. Hazard ratio more than 1 indicated that old patients had better survival outcome. CI, confidence interval; ER, estrogen receptor; NA, not available; PgR, progesterone receptor; TNBC, triple-negative breast cancer.Discussion Although there was no consensus definition for young breast cancer, it had been widely believed that breast cancer at a young age had a more aggressive biological behavior compared with the disease arising from older patients. Tumors in younger women present with a higher grade, a higher T stage, a higher N stage, and more dedifferentiation, and have a higher proliferating fraction and more vascular invasion 5,7–17. In our study, the clinicopathological characteristics of young patients were consistent with previous researches. Keegan et al.22 and Colleoni et al. 23 found that higher proportions of HER2-positive tumors occurred in young patients. It was reported that about 25% of all breast cancers are ER or PgR negative, but a large proportion of hormone receptor-negative tumors occur in young women 13,15,17,24. Azim et al. 11 reported that there was a significantly higher proportion of basal-like tumors (34.3%) in young patients compared with those aged 41–52 (27.7%). No significant differences in the breast cancer subtype pattern were observed in this study and this could be attributed to the limited sample size of our study. It has been shown that younger age was associated with a less favorable prognosis 5,7–17. Tang et al. 15 found that with a follow-up of 54 months, inferior 5-year DFS (72 vs. 83%, P<0.01) and 5-year OS (87 vs. 93%, P <0.01) were observed in patients aged younger than 40 years compared with those aged 40–50 years. In our study, worse 5-year DFS was observed in young patients (62.2 vs. 77.8%, P=0.037), which was consistent with the results in previous studies. Stratified analysis showed that the predictive value of age on DFS was proven in the subgroup of patients with high-risk factors, including inflammatory breast cancer, large primary tumor, positive axillary lymph node, or higher TNM tumor stage at diagnosis, whereas no difference in the 5-year DFS was observed in patients without the above-mentioned risk factors. Similarly, in the study of Han et al. 5, there was no significant difference in DFS between young and old groups in lymph node-negative patients (P=0.223), whereas the younger group showed worse prognosis among lymph node-positive patients (P<0.001). In a Korean study, patients in the very young group with lymph node metastasis had poorer 5-year OS (70 vs. 83%, P<0.001) and DFS (58 vs. 74%, P <0.001) than their older counterparts; in patients without lymph node metastasis, the survival outcomes did not differ significantly between the two groups 17. Therefore, it is a key point to identify high-risk young breast cancer patients, and implement a tailored and aggressive treatment to improve the outcomes of these patients. It had been reported that improved survival outcomes were observed in patients with pCR compared with those with residual tumor 18,25–29. Further analysis showed that pCR was associated with better DFS in ER or PgR-positive/HER2-negative with grades 1–2, HER2-positive, and triple-negative disease, but not for those with ER or PgR-positive/HER2-positive, and ER or PgR-positive/HER2-negative with grade 3 tumors 18. In addition, in a meta-regression analysis of 29 heterogeneous neoadjuvant trials, pCR was not suggested to be a surrogate end point for DFS and OS in patients with breast cancer 30. At the 2016 annual meeting of American Society of Clinical Oncology, Robidoux et al. 31 reported 5-year outcomes of the NSABP protocol B-41 and found that long-term outcomes correlated with pCR status. Additional analyses indicated that pCR was related to a significant improvement in survival rates in the ER-negative subset, but not in the ER-positive cohort. In our study, young patients achieving pCR showed similar 5-year DFS compared with those with non-pCR (P=0.408). Therefore, pCR may be not an appropriate surrogate for prognosis in young breast cancer patients treated with NCT. The TNM staging system maintained by the AJCC is considered the most clinically useful cancer staging system for cancers. Orucevic et al. 32 reported on 782 Caucasian women diagnosed with invasive ductal carcinoma who were grouped according to TNM stage and molecular phenotype. The results supported the traditional TNM staging as a continued relevant predictive tool for breast cancer outcomes even with the emerging prognostic impact of tumor biomarkers (ER/PgR/HER2). Carey et al.33 suggested that classification of residual tumor in the breast and axillary surgical specimens after NCT using the AJCC TNM staging system could predict distant relapse and survival. In our study, young patients with higher TNM stage at diagnosis showed worse survival outcomes. Therefore, TNM stage may be more predictive of prognosis than pCR in breast cancer patients treated with NCT. This study is limited by its retrospective nature, nonrandomized design, small sample size, and relatively short follow-up duration. Trastuzumab was not covered by medical insurance in China and was much more expensive than common chemotherapy drugs. Therefore, some of the HER2-positive patients could not afford the expense. The diversity of NCT regimens and difference in the proportions of patients receiving trastuzumab between young and old cohorts may also have influenced the results of this study. Further prospective studies are warranted to validate the results. In recent years, researches have confirmed that breast cancer arising in young women is a unique disease entity driven by complex biologic processes extending beyond hormone receptors and hereditary cancer syndromes. Anders et al. 34 found 367 significant gene sets among young women's tumors that specifically distinguished them from tumors arising in older women, including those related to immune function, the mammalian target of rapamycin/rapamycin pathway, hypoxia, BRCA1, stem cells, apoptosis, histone deacetylase, and multiple oncogenic signaling pathways. In the study of Azim et al. 11, breast cancer in the young was enriched with processes related to immature mammary epithelial cells and growth factor signaling. There was also downregulation of apoptosis-related genes. The identification of genomic pathways specific to breast cancer arising in young patients provided a better understanding of the interplay of age and contributing biologic processes and a unique opportunity to explore therapeutic targets. Conclusion Young breast cancer patients treated with NCT present more aggressive clinicopathological features and worse prognosis compared with their elderly counterparts. TNM stage at diagnosis may be more predictive of prognosis than pCR in young breast cancer patients with NCT. The underlying biology of young breast cancer needs to be elucidated and the development of tailored treatment is crucial. Acknowledgements The authors thank all doctors and nurses of the Department of Medical Oncology for their help with the realization of this study. Binghe Xu and Jiayu Wang designed the research, analyzed the data, and wrote the paper; Jingjing Wang analyzed the data and wrote the paper; Jiayu Wang, Qing Li, Pin Zhang, Peng Yuan, Fei Ma, Yang Luo, Ruigang Cai, Ying Fan, Shanshan Chen, Qiao Li, Binghe Xu selected the cases and analyzed the clinical data. Conflicts of interest There are no conflicts of interest.

Clinicopathological features and prognoses of very young patients (≤35 years) with breast cancer: a retrospective population-based study in China.

Breast cancer is very rare in young women and has a more aggressive biological behavior and a worse prognosis than in older premenopausal women. This study was designed to determine and evaluate the features of breast cancer in young patients less than 35 years old at the Instituto Nacional de Enfermedades Neoplásicas, Lima - Perú. Medical records of 115 patients less than 35 years old with breast cancer, whom were diagnosed and received a kind of treatment, even surgery, chemotherapy, radiotherapy or all of them at the Instituto Nacional de Enfermedades Neoplásicas Lima-Perú, between January 2000 and December 2012, were reviewed. Triple negative breast cancer (38.3%) is the most common subtype cancer and its presentation is in a lower age compared with the others subtypes (27.1 years vs 28.5 years p: 0.047). The high histological grade was more frequent in triple negative and HER2 subtypes (80% both vs 30% and 48% for luminal A and luminal B p: 0.001). The 2 yr and 5 yr overall survival was 75.0% and 59.3% for luminal A, 71.4% and 55.1% luminal B, 67.7% and 54.9% triple negative, 58.3% and 41.7% HER2 (p: 0.434). The 2 yr progression free survival was 81.6%, 72.6%, 61.5% and 59.4% for each group respectively (p: 0.522). As conclusion, the breast cancer in 35 yr old or less women is uncommon; the triple negative subtype is more common, also in relation with high histological grade and in lower age. The overall survival and the progression free survival are worse in patients with lower age. Citation Format: Morante ZD, Pacheco C, Limón RS, Neciosup S, Gomez HL. Breast cancer in young patients, twelve years of experience in a single institution. [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 P1-07-18.

Introduction: Breast cancer in young people (age ≤ 40), represents 5% of all breast cancer cases. Population outcomes for this group are often derived from subgroup analyses of randomized or retrospective trials. Limited data about physicians' knowledge, attitudes and practices as they relate to this diagnosis. The aim of our study was to evaluate the decision-making process in Latin-American oncologists for the treatment of young women with early breast cancer. Methods: A survey was designed with 30 items. Principal topics included: use of ovarian suppression, indication for adjuvant chemotherapy, fertility, use of genomic tests and recommendations for management of treatment-associated symptoms. Content validation was undertaken by Argentinian oncologists of SUMA (Argentinian Group for the treatment and research of breast cancer ). The study was conducted via an online questionnaire, sent by email to professional societies and to oncologists involved in the management of breast cancer patients. Descriptive analyses were included. Chi square test was performed to evaluate relationships between physician characteristics (country, gender, years of expertise, whether the physician worked in a tumor specific clinic or not) and responses. The level of statistical significance was set at p &amp;lt; 0.05, two-tailed. Results: A total of 329 Latin American oncologists from 17 Latin-American countries participated in the electronic survey. The responding oncologists included 74.5% who treated patients with any tumor type (ALLT), 14.6% specialized in breast and gynecological tumors (BRGY), and 10.9% focused exclusively on breast tumors (BREX). Working in a tumor-specific clinic was associated with differential utilization of several treatments or diagnostic tests, including ovarian suppression (OFS) for therapeutic purposes during neo/adjuvant chemotherapy (74.7% ALLT, 91.6% BRGY, 86.1% BREX; p=0.031), selective recommendation for OFS with endocrine therapy during the adjuvant setting (51.4% ALLT, 66.6% BRGY, 75% BREX; p &amp;lt; 0.001), and routine evaluations of FSH levels during treatment with OFS (70.5% ALLT, 86.8% BRGY, 86.2% BREX; p=0.038). Genetic counseling was always offered in young patients by 47.8%, 72.9% and 69.4% of physicians with ALLT, BRGY and BREX clinics, respectively (p=0.014). The use of genomic platforms for decision-making also differed: 55.6% of BREX oncologists reported always using these platforms in cases of young women compared to 38.8% of oncologists who treat all types of tumors (p &amp;lt;0.001). Specifically, chemotherapy was recommended to patients with recurrence score higher than 20 by 49%, 77.8% and 60.4% of oncologists with ALLT, BRGY and BREX clinics, respectively (p=0.003) The reported practices did not differ among professionals from different countries. Conclusions: According to the results of our survey the approach to managing early HR+ HER2- negative breast cancer in young women differ depending by professional focus. Full results will be presented. Further research is needed to understand the basis for these differences. However, given the heterogeneity of responses, our study highlights the need for specific guidelines for the management of breast cancer in young patients. Citation Format: Dana P. Narvaez, Federico Waisberg, Victoria Costanzo, Danilo Aguirre, Cynthia Villarreal, Matías Chacón, Sergio Rivero, Alexis Ostinelli, Fernando Namuche Ojeda, Alvaro Encinas Casanave, María Lucila González Donna, Cinthia Gauna, Juana Vazquez, María P. Molina Espinosa, Sara C. Altuna Mujica, Ronald Limón, Kayra K.Sanchez Muñoz, Claudia Martinez, Adrian Nervo, Gonzalo Gomez Abuin, Santiago Bella, Andrea Aguilar, Vanesa Lopez, Pablo Mandó, Valeria Caceres. Variability in physician treatment decisions for HR+ / HER 2 negative Early Breast Cancer in young patients: a Latin-American survey [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2024; 2024 Dec 10-13; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2025;31(12 Suppl):Abstract nr P4-11-15.

Background: Young breast cancer patients (pts) carrying a germline BRCA mutation (mBRCA) have similar outcomes as non-carriers. However, there is currently lack of evidence regarding the impact of mBRCA type and hormone receptor status on clinical behavior and outcomes of mBRCA breast cancer. We aim to address these questions in the largest dataset to date of young mBRCA breast cancer pts. Methods: This was an international, multicenter, hospital-based, retrospective cohort study. Women harboring deleterious germline mBRCA1 or mBRCA2 that received a diagnosis of stage I-III invasive early breast cancer at age ≤40 years between January 2000 and December 2012 were included. Baseline pts, tumor, and treatment characteristics, pattern and risk over time of disease-free survival (DFS) events, and survival outcomes (DFS, distant recurrence-free interval [DRFI] and overall survival [OS]) were compared between mBRCA1 and mBRCA2 pts overall and by hormone receptor status. Multivariate Cox proportional hazard models were used to compare hazard rates (HRs). Results: 1,236 young mBRCA breast cancer pts were included. Among 808 and 428 pts with mBRCA1 or mBRCA2, respectively, 191 (23.6%) and 356 (83.2%) had hormone receptor-positive tumors while 617 (76.4%) and 72 (16.8%) hormone receptor-negative disease (p&amp;lt;0.001). Compared to mBRCA2 breast cancer pts, those with mBRCA1 were younger, more likely to have reported Jewish ancestry, had more grade 3 tumors, less nodal involvement, lobular histology and HER2 positivity, and received more frequently chemotherapy (all p&amp;lt;0.001). More mBRCA1 pts with hormone receptor-positive tumors did not receive adjuvant endocrine therapy (14.7% vs. 4.2%, p&amp;lt;0.001). No difference between mBRCA1 and mBRCA2 pts was observed in risk-reducing mastectomy (43.9% vs. 46.0%; p=0.371) or salpingo-oophorectomy (48.3% vs. 48.8%; p=1.0). Median follow-up was 7.9 years (range 5.6-10.6 years). Second primary breast cancers (17.0% vs. 12.2%, p=0.025) and non-breast primary malignancies (4.3% vs. 1.9%, p=0.033) were more frequent among mBRCA1 pts compared to mBRCA2 pts, while distant recurrences were less frequent (10.4% vs. 15.4%, p=0.013). 8-year DFS was 62.8% and 65.9% for mBRCA1 and mBRCA2 pts, respectively (adjusted HR 0.76; 95% CI 0.60-0.96). The worse DFS in mBRCA1 was observed regardless of hormone receptor status (pinteraction=0.848): hormone receptor-positive (adjusted HR 0.77; 95% CI 0.58-1.03) and hormone receptor-negative (adjusted HR 0.73; 95% CI 0.48-1.13). No differences in DRFI and OS were observed between mBRCA1 and mBRCA2 pts. Compared to pts with hormone receptor-negative disease, those with hormone receptor-positive breast cancer had higher chances of developing distant (± loco-regional) recurrences (16.1% vs. 9.0%; p&amp;lt;0.001) and less frequent second primary malignancies (BC: 12.1% vs. 17.9%, p=0.005; non-BC: 2.8% vs. 4.0%, p=0.216). No differences in DFS and OS were observed between pts with hormone receptor-positive or negative breast cancer. However, there was a trend towards worse DRFI in women with hormone receptor-positive breast cancer as compared to those with hormone receptor-negative disease (8-year DRFI: 83.4% vs. 90.1%; adjusted HR 1.39; 95% CI 0.94-2.05). Conclusions: In this large unique dataset, young mBRCA1 breast cancer pts had worse DFS than those with mBRCA2 mostly due to higher rates of second primary malignancies. Hormone receptor positivity had no positive prognostic value in young mBRCA breast cancer pts with a trend towards worse DRFI in those with hormone receptor-negative disease. These results provide important information for counseling young mBRCA breast cancer pts regarding treatment, prevention and follow-up care strategies. Citation Format: Matteo Lambertini, Marcello Ceppi, Anne-Sophie Hamy, Olivier Caron, Philip D. Poorvu, Estela Carrasco, Albert Grinshpun, Kevin Punie, Christine Rousset-Jablonski, Alberta Ferrari, Shani Paluch-Shimon, Angela Toss, Claire Senechal, Fabio Puglisi, Katarzyna Pogoda, Jose Alejandro Pérez-Fidalgo, Laura De Marchis, Riccardo Ponzone, Luca Livraghi, Maria Del Pilar Estevez-Diz, Cynthia Villarreal-Garza, Maria Vittoria Dieci, Florian Clatot, Francois P. Duhoux, Rossella Graffeo, Luis Teixeira, Octavi Córdoba, Amir Sonnenblick, Arlindo R. Ferreira, Ann H. Partridge, Antonio Di Meglio, Claire Saule, Fedro A. Peccatori, Marco Bruzzone, Lucia Del Mastro, Lieveke Ameye, Judith Balmaña, Hatem A. Azim, Jr. Clinical behavior and outcomes of BRCA-mutated breast cancer in young patients according to type of BRCA mutation and hormone receptor status: Results from an international cohort study [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PD10-06.

BACKGROUND AND OBJECTIVES: Breast cancer in young patients (&amp;lt;= 40 years) (YBC) is an uncommon disease and is the leading cause of cancer death in women in their age. The objective of this study was to characterize and identify potential differences in the molecular and clinical features of breast carcinomas from patients &amp;lt;=40 years versus a cohort of older premenopausal counterparts as a control matched by breast cancer subtype. METHODS: We performed a retrospective analysis of a prospectively maintained database that included 427 premenopausal patients diagnosed with an invasive breast carcinoma from 2005 to 2013 at University of Tsukuba Hospital. We selected 286 patients separated in two groups, the study group with young women &amp;lt;=40 years old and with no or unknown BRCA mutation, and a second group with women over 40 years. Data related to clinical and pathological features from both groups such as tumor size, nodal status, histological grade, Ki 67 labeling index, estrogen and progesterone receptor, HER2 overexpression, and pregnancy related information were obtained from medical records and we used the statistic model of chi-squared to compare the two groups. Survival analysis was performed using the Kaplan Meier method. RESULTS: The median age of the 93 patients ≤ 40 year was 34.6 years, and 193 patients &amp;gt;40 years were included in the control group (median age 46.4 years). There were 22 pregnancy associated breast cancer (PABC) cases in YBC cohort. Ductal carcinoma was the most common histological subtype in both groups. By subtype, 65% of YBC presented an immunohistochemical luminal subtype, compared to 41% in PABC and 77% in older patients (p=0.01). Triple negative and HER2 profiles were 19% and 16% in YBC versus 36% and 23% in PABC and 12% and 11% in control respectively (p=0.01). The YBC cohort had a larger tumor (24% of YBC had size tumor &amp;gt; 5 cm, versus 9% in control, p=0.01), and more frequent nodal involvement (48% in YBC vs 39% in control, p&amp;lt;0.05), the higher proportion of Ki67 &amp;gt;30% (35% in YBC vs 24% in control, p&amp;lt;0.05). Limiting to YBC, subtype nor PABC were not identified as an independent risk factor for disease free survival, but luminal subtype in YBC demonstrated worse survival compared with those in control. CONCLUSIONS: We observed more aggressive tumor characteristics in patients diagnosed with breast cancer at &amp;lt;=40 years, or PABC patients compared to older premenopausal patients. Clinical implications of age on tumor behavior were different according to subtypes. Further research to overcome worse survival for luminal YBC is warranted. Citation Format: Hiroko Bando, Mai Furuya, Aya Sawa, Akiko Iguchi, Tatsuhiko Ikeda, Shotaro Shima, Hisato Hara. Characterization of of the tumor and risk factors in Japanese young breast cancer patients [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P6-10-16.

Objectives and rationale: Breast cancer (BC) arising at a young age is relatively uncommon; however, approximately 6 to 10% of women diagnosed with BC are younger than the age 40. This subgroup of young women presents different risk factors, tumor biology, and clinical outcomes. Moreover, the interpretation of the effects of inherited genetic factors on the prognosis of young patients with BC remains a subject of debate. The primary aim of this study was to evaluate the characteristics of young patients with BC and to compare the long-term oncological results between BRCA-mutation carriers and non-carriers. We retrospectively reviewed all the consecutive young (≤ 40 years old) BC patients treated at the Breast Unit of IRCCS Humanitas Research Hospital (Milan, Italy). All young patients underwent BRCA-mutation analysis. For further analysis young BC patients were divided into two groups: BRCA-mutation carriers versus non-carriers. Tumor, surgical treatment, and post-operative data were compared between the two groups. Primary end-points were: disease-free survival (DFS), distant disease-free survival (DDFS), and overall survival (OS). The Kaplan-Meier method was used to generate the recurrence and survival curves. Multivariate analyses were performed using the Cox proportional hazards model to identify independent risk and protective factors for DFS, DDFS, and OS. Results: The characteristics of 63 young BC patients with BRCA-mutation were compared with 339 young BC patients without BRCA-mutation. BRCA-mutation carriers tend to be younger (60.3% versus 34.8% if age ≤ 35 years, odds ratio (OR) = 17.699, 95% confidence interval (95%CI) = 33.871-35.568, p = 0.001) and present more aggressive tumors (66.7% versus 40.7% if G3, OR = 17.119, 95%CI = 2.549-2.828, p = 0.001; 57.2% versus 12.4% if biological subtype triple negative, OR = 52.727, 95%CI = 2.042-2.417, p = 0.001; 73.0% versus 39.2% if Ki67 ≥ 25%, OR = 58.981, 95%CI = 47.135-58.505, p = 0.001). Young BC patients without BRCA-mutation presented significantly better long-term oncological results in terms of DFS, DDFS, and OS compared with young BRCA-mutation carriers (10-years DFS rate 91.1% versus 58.1%, p &amp;lt; 0.001; 10-year DDFS rate 91.2% versus 76.1%, p = 0.003; 10-year OS rate 98.0% versus 87.8%, p = 0.002, respectively). Neo-adjuvant chemotherapy was found to be an independent protective factor for OS in young BRCA-mutated BC patients (hazard radio = 14.885, 95%CI = 2.343-94.566, p = 0.004). Conclusions: Breast cancer is more likely to present at a younger age (≤ 35 years) and with more aggressive characteristics (G3, triple negative, Ki67 ≥ 25%) in patients with BRCA-mutation compared with their non-mutated counterpart. Young BRCA-mutation carriers show a poorer prognosis in terms of recurrence and survival compared with non-carriers. The implementation of neo-adjuvant chemotherapy may improve survival in young BC patients with BRCA-mutation. Citation Format: Damiano Gentile, Simone Di Maria Grimaldi, Andrea Sagona, Erika Barbieri, Alberto Bottini, Giuseppe Canavese, Giulia Caraceni, Shadya Darwish, Corrado Tinterri. Comparison of long-term oncological outcomes in young women with breast cancer between BRCA-mutation carriers versus non-carriers: How genetic risk factors and tumor characteristics influence the prognosis [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO5-22-08.

Correlation Between Clinical-Pathologic Factors and Long-Term Follow-Up in Young Breast Cancer Patients

Mammography and Breast Localization for the Interventionalist

Introduction Breast tumors (BC) in young patients is frequently diagnosed as a high-grade tumor, at a more advanced stage, hormone receptor negative and Her2 overexpressed. Age is an important risk factor for local recurrence, despite the type of surgery, and is associated to increased risk of metastasis and death. Neoadjuvant Chemotherapy (NeoCT) is the standard of treatment for locally advanced and higher risk tumors (triple negative/TN and HER2 positive). Objectives Observation of BC and prognostic factors in young women submitted to NeoCT in a Brazilian cancer center and to compare age groups (31-40 years of age and below 30 years). Method Retrospective cohort study of women with BC diagnosed at below the age of 40, submitted to NeoCT at a Brazilian cancer center, between 2000-2016. The Residual Cancer Burden (RCB) was used for analysis of the pathological response. P &amp;lt;0.05 was considered statistically significant for Pearson's Chi-square test and Fisher's exact test. Survival analyses were estimated by Kaplan-Meier and the patients were followed for at least 60 months. Results 271 women with BC under the age of 40 were submitted to NeoCT. Of these patients, the age of 217 (80.1%) was between 31-40 years of age, 54 (19.9%) were below 30, and 29.2% had family history of BC or ovarian cancer in first or second degree relatives. Data for clinical staging was 2.2% stage I, 43.1% II, 52.4% III and 2.2% IV (as a single site metastasis). We identified a difference in the stage IV group, with 7.4% (4/54) in the women younger than 30 years and 2.2% (6/217) in the women 31-40 years of age (p 0.035). The most frequent histology was invasive ductal carcinoma, in 87.5% of cases, with histological grades of 2 (35.8%) and 3 (46.9%). Histological subtype revealed 49.1% luminal, 17.7% luminal with 2 superexpressions, 8.1% HER2 and 24.4% TN. We identified a greater proportion of luminal patients in the 31-40 year range (53.9% vs 30.8%) and TN and Her2 in the group younger than 30 years (32.7% and 36.5% vs 22.6% and 23.5%, respectively), p 0.006. Chemotherapy based on anthracyclines and taxanes was used in 76.3% of the cases, with HER2 block when indicated. Dense dose schedules were used in 9.6% of the cases. Complete pathological response (pCR) occurred in 34.7% of the cases, partial response in 45.4%, stable disease in 11.1% and progression during chemotherapy in 1.5% of the cases (2 TN and 2 luminal), not revealing any trend as per age group. Her2 tumors had pCR of 63%, 55% for Her2 luminal, and 53.7% for TN. Conservative surgeries were performed in 78 patients (28.8%) and mastectomies in 193 (71.2%). Sentinel lymph node biopsy was performed in 20.7% of the cases, and lymphadenectomy in 79.3%. 56.9% of patients with conservative surgery and 29.6% of those submitted to mastectomy with pCR. Even with pCR, 94 cases (56.3%) were mastectomized. Of the 251 patients, 37.6% relapsed, 21% distant recurrence, 7% local and 9.1% local and distant, with no variation regarding age group. Of these, 23.1% underwent conservative surgery and 37.4% underwent mastectomy. The response is actually inversely correlated with 15% of patients with pCR, 39.8% of partial responses, 63% of stable diseases and 75% disease progression during treatment. Overall survival was associated to a pathological response, tending to benefit the age range of 31-40 years. Conclusions BC in young patients may have reveal differences as per their age group. In our sample, patients under the age of 30 revealed the most advanced and most aggressive subtypes of BC when compared to women in the 31-40 year group. No distinction was made between NeoCT and relapse, however a survival trend was observed in patients over 30 years of age. No distinction was made between RCB and relapse, but there was a trend of survival in patients over 30 years. Citation Format: Lilian Fraianella, Silvana S Santos, Solange M Sanches, Caroline GA Rocha, Marina De Brot, Fabiana BaroniAlves Makdissi. Breast cancer in young patients undergoing neoadjuvant chemotherapy - A comparison between very young women (less than 30) and young women (31-40 years) - Experience of a cancer center in Brazil [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P2-08-28.

IntroductionThe aim of this study was to compare epidemiological characteristics of breast cancer in young adolescent women (YAW) versus older women (OW).MethodsThis was a cross-sectional prospective observational study, conducted in Ward 3, Jinnah Postgraduate Medical Center, Karachi, Pakistan, from September 2021 to February 2022. A total of 120 female patients were recruited in this study from the Outpatient Department of Jinnah Postgraduate Medical Center, out of which 22 patients were below the age of 40 years and 98 were above 40 years. For breast cancer diagnosis, we used the triple assessment method involving clinical examination, radiology, and histopathology. Diagnosed patients were further evaluated for hormonal status and metastatic workup. Results were noted on a performa, and differences between both age groups were analyzed.ResultsOut of 120 patients, 22 were younger than 40 years and 98 were older than 40 years. YAW used to present late after the appearance of symptoms. Patients of both age groups mostly presented with breast lumps (68.18% in YAW and 81.6% in OW). YAW presented with larger sizes of lumps and with more nodal involvement as compared to OW. BI-RADS IV (Breast Imaging Reporting and Data System Category IV) was the most commonly observed (27.27% in YAW and 48.97% in OW) mammographic finding in both age groups. Invasive ductal carcinoma was the most common histological type in both age groups (72.73% in YAW and 76.53% in OW). The triple-negative disease was more commonly found in YAW than OW (40.91% in YAW vs 21.43% in OW). We found that usually YAW presented at advanced stages (stages III and IV, 54.55%) and higher grades (grade III, 63.63%).ConclusionBreast cancer in young patients is rare but more aggressive with higher grades, advanced stages, and poor prognostic features. Heredity is mainly the risk factor in young breast cancer patients. There should be proper screening programs for high-risk group for early diagnosis and prompt treatment. Other age-specific concerns such as psychological impact of disease should be addressed as well.

BACKGROUND AND OBJECTIVES:Despite its relatively low incidence in Saudi Arabia, breast cancer has been the most common cancer among Saudi females for the past 12 consecutive years. The objective of this study was to report the results of the first national public breast cancer screening program in Saudi Arabia.METHODS:Women 40 years of age or older underwent breast cancer screening. Mammograms were scored using the Breast Imaging-Reporting and Data System (BI-RADS). Correlations between imaging findings, risk factors and pathological findings were analyzed.RESULTS:Between September 2007 and April 2008, 1215 women were enrolled. The median age was 45 years, and median body mass index was 31.6 kg/m2. Sixteen cases of cancer were diagnosed. No cancer was diagnosed in 942 women with R1/R2 scores, and only 1 case of cancer was diagnosed in 228 women with R0/R3 scores. However, among 26 women with R4/R5 scores, 50% had malignant disease and 35% had benign lesions. No correlation was found between known risk factors and imaging score or cancer diagnosis.CONCLUSIONS:Public acceptance of the breast cancer screening program was encouraging. Longitudinal follow-up will help in better determining the risk factors relevant to our patient population.

It has been known that young breast cancer patients have worse outcomes compared with older premenopausal or postmenopausal patients. Survival difference between young and older breast cancer patients is evident only in hormone receptor positive breast cancer regardless of tamoxifen treatment according to our previous report. However, the biology of aggressiveness and endocrine resistance of breast cancer in very young women is largely unknown. The purpose of this study is to find molecular characteristics of hormone receptor positive breast cancers of very young age women (&amp;lt;35) compared with those of older premenopausal women. We extracted mRNA from fresh frozen hormone receptor positive primary breast cancer tissues of 24 young age breast cancer patients (&amp;lt;35 years) and 31 older premenopausal women (40 to 49 years) by standard method. All tumor specimens analyzed contained more than 50% tumor cells. Hormone receptor status was determined by immunohistochemistry (IHC). Gene expression microarray experiment was done in the 55 samples using Illumina HumanRef-8 v3 Expression BeadChip (Illumina, Inc., San Diego, CA). Functional and pathway analysis of differentially expressed genes were done using DAVID (http://david.abcc.ncifcrf.gov/home.jsp) and Ingenuity pathway analysis (IPA, http://www.ingenuity.com). Ki-67 assay was done using IHC in 4,957 ER+ breast cancer patients of Seoul National University cohort and 1,863 ER+ patients from National Cancer Center, Korea. 355 genes were upregulated (&amp;gt;1.5 fold) and 209 genes were down-regulated in breast cancer tissues of young age patients (&amp;lt;35) compared with those of older patients. In pathway analysis of the highly expressed genes in young patients, cell cycle function and pathway was significantly activated. The genes of central role in this pathway were MYC and CCND1. In IHC assay for 4,957 ER+ Seoul National University dataset, the proportion of high Ki-67 expression (&amp;gt;=10%) was positively correlated with decreasing age: 26.4%, 24.0%, 21.3%, 14.8%, 12.0% of women aged &amp;lt;30, 30–34, 35–39, 40–49, 50–59, respectively (p&amp;lt;0.001). The same correlation pattern between younger age and high Ki-67 expression was also seen in another 1,863 patient cohort. In conclusion, we showed that genes involved in cell cycle pathway were upregulated in very young age (&amp;lt;35) ER+ breast cancer using microarray study. It was validated in large data set using Ki-67 IHC assay. High proliferation and fast cell cycle could be a mechanism of worse outcome and tamoxifen resistance of ER+ very young age breast cancer patients. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P4-01-13.

Prognosis of breast cancer depends on classic pathological factors and also tumor angiogenesis. This study aimed to evaluate the clinicopathological factors of breast cancer in a tertiary centre with a focus on the relationship between tumor angiogenesis and clinicopathological factors. Clinicopathological data were retrieved from the archived formal pathology reports for surgical specimens diagnosed as invasive ductal carcinoma, NOS. Microvessels were immunohistochemically stained with anti-CD34 antibody and quantified as microvessel density. At least 50% of 94 cases of invasive breast ductal carcinoma in the study were advanced stage. The majority had poor prognosis factors such as tumor size larger than 50mm (48.9%), positive lymph node metastasis (60.6%), and tumor grade III (52.1%). Higher percentages of estrogen and progesterone receptor negative cases were recorded (46.8% and 46.8% respectively). Her-2 overexpression cases and triple negative breast cancers constituted 24.5% and 22.3% respectively. Significantly higher microvessel density was observed in the younger patient age group (p=0.012). There were no significant associations between microvessel density and other clinicopathological factors (p>0.05). Majority of the breast cancer patients of this institution had advanced stage disease with poorer prognostic factors as compared to other local and western studies. Breast cancer in younger patients might be more proangiogenic.