Determinants of patient delay and its association with quality of life among young women with breast cancer in China: A cross-sectional study.

Breast cancer, menopause, and long-term survivorship: critical issues for the 21st century

Breast cancer in young women: challenges, progress, and barriers.

Breast cancer in women aged younger than 35 years old comprises approximately 3 % of Japanese breast cancer patients [1]. Interestingly, the estimated breast cancer incidence in young women under 40 years of age is approximately 25 per 100,000 women be it in Japan or the USA or the European Union, whereas breast cancer incidence in all ages is higher in Western than in Asian countries [2]. Younger women with breast cancer are known to have worse prognoses than their older counterparts [3, 4]. The worse prognosis may be because greater numbers of younger women have tumors with poor clinicopathological features, i.e., more advanced TNM stage at presentation and more hormone receptor negative tumors as demonstrated in previous studies [1, 5]. The underlying biology of breast cancer in the young woman has yet to be fully elucidated. Association with age-related biological processes, such as pregnancy, parity, and breast-feeding, has been suggested to have prognostic impact in clinical and preclinical studies [6, 7, 8]. Adjuvant chemotherapy is used more frequently in young women than in older women [1], probably because of longer life-expectancy and better tolerability to aggressive treatments and documented survival advantages compared to women not treated with adjuvant therapy. Recently, the ATLAS and aTTom trials have demonstrated statistically significant superiority of adjuvant tamoxifen of 10 years duration compared to that of 5 years [9, 10]. Biases that ‘‘young women have worse prognosis’’ and the fear of the disease with its accompanying threat to life that it instils in patients as well as healthcare providers might lead to overuse of ‘‘one-size-fits-all’’ chemotherapy and endocrine therapy demonstrated to be of clinical benefit in randomized clinical trials. However, we have to be aware that this approach may well affect patient quality of life once a patient becomes a survivor. For example, treatmentrelated infertility is one of the major concerns of cancer patients of reproductive age [11]. In this issue of Breast Cancer, topics specific to breast cancer in young women were selected in the hope that readers might gain some insights into optimization of the care of the young breast cancer patient and future research needs for this group. Kataoka et al. [1] provide a crosssectional data analysis of breast cancer in young Japanese women by utilizing the database of the Japanese Breast Cancer Society. They confirm that younger women in Japan present with larger tumors, more advanced disease stage, and a greater proportion of triple negative and HER2? tumors. Suggestions for research to be developed and the results of formal prognostic analyses to help guide these efforts are awaited. Shien et al. [12] summarized the current status of fertility preservation in breast cancer patients in Japan. They provide a review of available options and a framework for clinical discussion with the patient. Regardless of family history, in Western countries, manifestation of breast cancer in younger women is utilized as a criterion for recommendation of genetic counseling [13]. Bando reviews the problems to be addressed and resolved in Japan, where clinical genetic services are still immature [14]. The issues of lack of data, social concerns, and availability of clinicians with good knowledge regarding genetics are noted. Finally and importantly, Takahashi warns that psychosocial distresses of young women with breast cancer extends beyond genuine physical medical issues [15]. C. Shimizu (&) Breast and Medical Oncology Division, National Cancer Center Hospital, Chuo-ku, Japan e-mail: cshimizu@ncc.go.jp

The overall incidence of breast cancer in South Asian countries, including Nepal, is low compared to Western countries. However, the incidence of breast cancer among young women is relatively high. Breast cancer in such cases is characterized by a relatively unfavorable prognosis and unusual pathological features. The aim of this study was to investigate clinico-pathological and biological characteristics in younger breast cancer patients (<40 years) and compare these with their older counterparts. Nine hundred and forty four consecutive female breast cancer patients, admitted to the Department of Surgery, Tribhuvan University Teaching Hospital, Kathmandu, Nepal between November 1997 and October 2012, were retrospectively analyzed. Out of the 944 female breast cancer patients, 263 (27.9%) were <40 years. The mean age was 34.6 ± 5.0 years among younger patients compared to 54.1 ± 9.9 for those ≥ 40 years. The mean age at menarche was also significantly lower (13.5 ± 1.5 vs 14.2 ± 1.5 years p=0.001) while the mean duration of symptoms was significantly longer (7.6 vs 6.5 months p=0.004). Family history of breast cancer was evident in 3.0% of the young women versus 0.3% in the older one. Mammography was performed less frequently in younger patients (59.7%), compared to older (74.4%), and was of diagnostic benefit in only 20% of younger patients compared to 85% of older ones. At diagnosis, the mean tumor diameter was significantly larger in young women (5.0 ± 2.5 vs 4.5 ± 2.4 cm, p=0.005). Axillary lymph nodes were positive in 73% of younger patients and 59% of older patients. In the younger group, the proportion of stage III or IV disease was higher (55.1% vs 47.1%, p ≤ 0.05). The proportion of breast conserving surgery was higher in young patients (25.1% vs 8.7%) and a higher proportion of younger patients receive neoadjuvant chemotherapy (9.9% vs 2.8%). The most common histological type was ductal carcinoma (93.1% vs 86%). The proportion of histological grade II or III was higher in younger patients (55.9% vs 24.5%). Similarly, in the younger group, lymphatic and vascular invasion was more common (63.2% vs 34.3% and 39.8% vs 25.4%, respectively). Patients in the younger age group exhibited lower estrogen and/ or progesterone receptor positivity (34.7% vs 49.8%). Although statistically not significant, the proportion of triple negative tumors in younger age group was higher (22.4% vs 13.6%). Breast cancer in young Nepalese women represents over one quarter of all female breast cancers, many being diagnosed at an advanced stage. Tumors in young women exhibit more aggressive biological features. Hence, breast cancer in young women is worth special attention for earlier detection.

Age standardized incidence rates of breast cancer in developed countries is nearly threefold higher than in developing countries. Iran has had one of the lowest incidence rates for breast cancer in the world, but during the last four decades increasing incidence rates of breast cancer made it the most prevalent cancer in Iranian women. After adjustment for age, Iranian young women are at relatively higher risk of breast cancer than their counterparts in developed countries. The purpose of this study was to investigate some established risk factors of breast cancer in Iranian young women. A hospital-based case control study comprising 521 women with histologically confirmed, incident breast cancer and 521 controls frequency-matched by age and province of residence was conducted. Logistic regression performed to investigate associations of reproductive and anthropometric factors with breast cancer risk. In multivariate analysis, family history [odds ratio (OR): 1.61; 95% confidence interval (CI): 1.07-2.42], oral contraceptives (OC) usage (OR: 1.52; 95% CI: 1.11-2.08), low parity (OR parity ≥ 3 vs. 1-2: 0.33; 95% CI: 0.23-0.49), employment (OR: 1.83; 95% CI: 1.05-3.23) and shorter period of breast feeding (OR ≥ 37 months vs. < 37: 0.61; 95% CI: 0.44-0.84) were related to a higher risk of breast cancer in young women. This was the first study focusing on risk factors of breast cancer in Iranian young women. The trend of decreasing parity and shortened duration of breast feeding along with OC usage might partly explain the rapid rising of breast cancer incidence in Iranian young women.

The prognosis of breast cancer (BC) in young women (BCYW) aged ≤40 years tends to be poorer than that in older patients due to aggressive phenotypes, late diagnosis, distinct biologic, and poorly understood genomic features of BCYW. Considering the estimated predisposition of only approximately 15% of the BC population to BC-promoting genes, the underlying reasons for an increased occurrence of BCYW, at large, cannot be completely explained based on general risk factors for BC. This underscores the need for the development of next-generation of tissue- and body fluid-based prognostic and predictive biomarkers for BCYW. Here, we identified the genes associated with BCYW with a particular focus on the age, intrinsic BC subtypes, matched normal or normal breast tissues, and BC laterality. In young women with BC, we observed dysregulation of age-associated cancer-relevant gene sets in both cancer and normal breast tissues, sub-sets of which substantially affected the overall survival (OS) or relapse-free survival (RFS) of patients with BC and exhibited statically significant correlations with several gene modules associated with cellular processes such as the stroma, immune responses, mitotic progression, early response, and steroid responses. For example, high expression of COL1A2, COL5A2, COL5A1, NPY1R, and KIAA1644 mRNAs in the BC and normal breast tissues from young women correlated with a substantial reduction in the OS and RFS of BC patients with increased levels of these exemplified genes. Many of the genes upregulated in BCYW were overexpressed or underexpressed in normal breast tissues, which might provide clues regarding the potential involvement of such genes in the development of BC later in life. Many of BCYW-associated gene products were also found in the extracellular microvesicles/exosomes secreted from breast and other cancer cell-types as well as in body fluids such as urine, saliva, breast milk, and plasma, raising the possibility of using such approaches in the development of non-invasive, predictive and prognostic biomarkers. In conclusion, the findings of this study delineated the pathogenomics of BCYW, providing clues for future exploration of the potential predictive and prognostic importance of candidate BCYW molecules and research strategies as well as a rationale to undertake a prospective clinical study to examine some of testable hypotheses presented here. In addition, the results presented here provide a framework to bring out the importance of geographical disparities, to overcome the current bottlenecks in BCYW, and to make the next quantum leap for sporadic BCYW research and treatment.

Sir, Several studies have reported that high-risk human papillomaviruses (HPVs) are present in more than 50% of human breast cancers (Yu et al, 2000; Liu et al, 2001; Damin et al, 2004; de Villiers et al, 2005; Kan et al, 2005; Lawson et al, 2006a, 2006b; Yasmeen et al, 2007a, 2007b). Furthermore, high-risk HPVs of the same type were found in both cervical and breast cancer of the same patients (Hennig et al, 1999; Widschwendter et al, 2004). This finding has led to the hypothesis that HPVs could be transmitted to the breast through sexual activities (Kan et al, 2005; Lawson et al, 2006a, 2006b). Consequently, it is possible that the incidence of HPV-positive breast cancer in young women is related to high-risk HPV genital infections, which are much more common in young women who have multiple sexual partners (IARC, 1995). There are three studies concerning the age of women in relation to the incidence of high-risk HPV-positive breast cancer. While there were no differences in the average age of women with either HPV-positive or -negative breast cancer in Brazilian women (Damin et al, 2004). In contrast, two recent studies reported that the average age of HPV-positive breast cancer in Greek and Australian women are 38 and 55.6 years in comparison with HPV-negative breast cancer, which are 53 and 63.8 years (P=0.001 and 0.049), respectively, (Kroupis et al, 2006; Lawson et al, 2006a, 2006b). We recently reported that E6/E7 of HPV type 16 is present in the majority of invasive and metastatic breast cancer in comparison to normal mammary tissues in young Canadian women (Yasmeen et al, 2007a, 2007b). Moreover, we were able to demonstrate that the presence of E6/E7 of high-risk HPVs is correlated with invasive breast cancer in young Syrian women (Akil et al, in preparation); in this study, we documented the ages of Canadian and Syrian women in relation to their HPVs status. We found a statistically significant difference between the average age of women with high-risk HPV-positive breast cancers, which was 46.5 years in comparison with HPV-negative breast cancers of 57.5 years (P=0.05). Our data suggest that high-risk HPV-positive breast cancers are more frequent in younger women who are probably sexually more active than older women who have less sexual activity; thus, we firmly believe that high-risk HPV infections can be transmitted by sexual activity and could play an important role in the progression of human breast cancer. However, future epidemiological studies are necessary to confirm these findings.

Introduction:Breast cancer in young women is usually considered as breast cancer occurring in women younger than 40 years and is the most frequent cancer-related cause of death in these patients. In the past few years, there seems to be an increasing trend in the prevalence of breast cancer in young women, which, associated with poorer prognosis, more aggressive histologic features, and more frequent recurrence rates, makes it a rising threat to young women. This study aimed to evaluate the biological behavior of breast cancer in young women in our institution.Material and methods:A retrospective, unicentric, cohort study was conducted between 2012 and 2016. All consecutive patients with breast cancer were enrolled in the study. Cases were divided into two groups: case group, those younger than 40 years, and control group, those 40 years or older. The exclusion criterion was nonoperative treatment. Several clinical and pathologic parameters were evaluated, as well as were overall survival time and disease-free survival time.Results:The incidence of breast cancer in young women presented a rising tendency over the study period. Significant differences were observed in the comparison of the groups according to body mass index, age at menarche, age at birth of the first child, and proliferation rate. There were no differences in overall survival and disease-free survival rates between the groups.Conclusions:Young women had a more symptomatic presentation, a greater tumor proliferation rate, but similar outcomes compared with older patients. Greater multicentric studies are needed to confirm or refute these results.

Background: Breast cancer is the frequent neoplasia in young women, which in developing countries is associated with more adverse outcomes. In Latin America, reports have shown an increased incidence of breast cancer in young women. No information exist regarding breast cancer characteristics in young Guatemalan women. We aimed to describe the clinical-pathological features among women aged 45 years or less treated in a tertiary-level hospital in Guatemala. Methods: We examined data from 119 women aged 45 years or less diagnosed with primary invasive breast cancer at the Oncology Unit Roosevelt Hospital in Guatemala between 2016 and 2020. Data were drawn from medical files on sociodemographic characteristics, histology, clinical stage, and breast cancer subtypes.Results: Of the total sample, breast cancer in women aged 45 years or less represented 31.2% of the cases. Of these, 24.36% is before 35 years, 28.57% between 35 to 39 years, and 47.05% between 39 to 45 years. Advanced clinical stages affected 66.6% of young women (48.33% for stages III and 18.33% stage IV). Data from specific breast cancer molecular subtype showed that 72.35% of cases in young women expressed an aggressive molecular subtype (Her-2 positive 27.06%, triple-negative 21.76%, and luminal/Her-2 positive 23.53%). Regarding treatment, most young patients received surgical treatment, as well as neoadjuvant or adjuvant chemotherapy. Only 24.37% received hormonal and 26.89% radiation therapy. Conclusions: Our finding suggested that young women treated for breast cancer at a tertiary-level hospital in Guatemala had a high proportion of aggressive molecular subtypes and a high rate of locally advanced disease. This aggressive cancer behavior among young women is consistent with findings in other Latin American countries. Evidence examining risk factors for aggressive cancer in young women, such as delay in diagnosis and treatment timing, is warranted. Table 1. Distributions of socio-demographic and cancer-related characteristics variables% (SE)n = 119ETHNIC GROUPMayan Indigenous12.61 (3.05)No-Mayan Indigenous87.39 (3.05)HISTOLOGYDuctal96.64 (1.66)Lobular1.68 (1.18)Other1.68 (1.18)CLINICAL STAGE*I1.67 (1.17)II31.67 (4.26)III48.33 (4.58)IV18.33 (3.54)BREAST CANCER SUBTYPELuminal27.65 (4.76)Her2 positive27.06 (5.11)Triple-negative21.76 (5.05)Luminal/Her223.53 (6.61)TREATMENTSurgery55.46 (4.58)Neoadjuvant Chemotherapy82.35 (3.51)Adjuvant Chemotherapy47.06 (4.59)Radiotherapy26.89 (4.08)Hormonotherapy24.37 (3.95) Citation Format: Juan F Alvarado-Muñoz, Agatha Reyes-Morales, Alba J Kihn-Alarcón, Marco Chivalan, Silvana Torselli, Victor Puac-Polanco. Breast cancer in young women in a tertiary-level hospital in Guatemala [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 PS7-64.

117 Background: Young Survival Coalition (YSC) is the premier global organization dedicated to the critical issues unique to young women and breast cancer. In May, 2014, YSC released its Research Agenda which identified the most pressing research questions that must be answered in order to improve the quantity and quality of life for young women affected by breast cancer. Methods: This Research Agenda arose out of an almost two-year-long process created and facilitated by YSC, called the Research Think Tank (RTT). YSC assembled doctors, researchers and advocates to focus on six areas of particular importance to its young constituents: risk factors; treatment; metastasis; quality of life; fertility; and pregnancy. Results: Through the work of the RTT, YSC assessed the current state of knowledge as well as existing gaps in each of the six identified areas. While work is needed in all areas, there have been recent updates and progress regarding treatment and fertility. Additionally, quality of life studies examine the uniqueness of breast cancer in young women, although application of this knowledge through tested interventions, decision aids, or guidelines and tools for physicians are still lacking. Aspects of pregnancy during breast cancer and after breast cancer have been studied but many open questions remain. There has been little progress in understanding why so many breast cancers are diagnosed in the postpartum period, why they tend to be more aggressive, and what can be done to prevent or treat it. Research examining metastasis in young women is rare. Most research focuses on postmenopausal patients, and many studies set criteria that specifically exclude younger women. This is the topic area most in need of work and priority. Similarly, little research focuses on the specific risk factors for early onset breast cancer. These are likely distinct from the risk factors associated with postmenopausal breast cancer yet they are rarely separately examined. Conclusions: Compared to older women, young women generally face more aggressive cancers, lower survival rates, and unique psychosocial concerns. Breast cancer in young women is an area in need of additional work and clarification in order to increase their quantity and quality of life.

Breast cancer (BC) in young women is rare, affecting only 4-6% of women under the age of 40. Regardless, BC remains the most common malignancy among younger patients. Recently, a significant increase in BC rates has been observed among pre-menopausal subjects. Breast cancer in young women requires special attention due to its specific morphologic and prognostic characteristics and unique aspects, including fertility preservation and psychosocial issues (e.g. its impact on family life and career). Young women are more likely to have tumors with higher incidence of negative clinicopathologic features (higher histological grade, more lymph node positivity, lower estrogen receptor (ER) positivity, higher rates of Her2/neu overexpression). Also, they tend to be diagnosed at more advanced stages of the disease. That, in turn, contributes to less favorable prognosis as compared to older women. Young women are generally treated similarly to older patients. Surgical management includes mastectomy or breast-conserving surgery, followed by radiation therapy (younger women have higher local recurrence rates than older women, especially after breast-conserving therapy). Although the basics of chemotherapy are the same for patients of all ages, younger women have some special considerations. It is important to consider options for fertility preservation before starting systemic treatment. Patients should have access to genetic testing as their results may affect the choice of therapy. Younger women and their families should receive adequate psychological support and counselling.

The global incidence of hormone-positive breast cancer (HR+ BC) in young women is rising, though the underlying reasons remain unclear. HR+ disease in younger women appears to represent a distinct clinical entity compared to that in older women, exhibiting distinct clinicopathological characteristics, outcomes and responses to treatment. Despite these differences, there is a paucity of large-volume data focusing on young women with HR+ in contemporary literature. Hormone receptor positive breast cancer in young women is associated with poorer prognoses compared to older women. Additionally, early age onset breast cancer presents unique challenges, including concerns related to fertility, the toxic effects of therapeutic agents, and specific surgical considerations. The purpose of this review is to report the existing literature on HR+ disease in young women.

Invited Commentary: The Challenges of Early-Onset Breast Cancer.

Breast cancer in young women (< 40 years) is rare and carries a poor prognosis relative to breast cancer in older women. Most studies examining global breast cancer patterns do not describe the trends in young women specifically. Data from GLOBOCAN 2018 were used to compare breast cancer incidence and mortality rates among younger (ages 0-39) vs. older (ages 40+) women across 185 countries. The coefficient of variation (the ratio of the standard deviation to the mean) was used to quantify relative variability. The risk of developing breast cancer to age 39 ranged from 0.13% in Guinea to 0.95% in South Korea (coefficient of variation: 46%), and the risk of death from breast cancer to age 39 ranged from 0.02% in China to 0.72% in Cameroon (coefficient of variation: 81%). In contrast, the risk of developing breast cancer to age 74 ranged from 1.5% in Mozambique to 12.2% in Belgium (coefficient of variation: 50%), and the risk of death from breast cancer to age 74 ranged from 0.65% in South Korea to 3.0% in Somalia (coefficient of variation: 36%). Among young women, breast cancer mortality rates varied more worldwide than breast cancer incidence. In contrast, among older women/women of all ages, breast cancer incidence varied more than breast cancer mortality. Further research is required to examine the impact of stage at diagnosis, clinicopathologic features, and treatments received, on variations in the survival and mortality of breast cancer in young women around the world.

Objective. To investigate and compare aspects of breast cancer in young women (&lt;40 years old) with older women (&gt;40 years old). Methods. Retrospective, cross-sectional, analytical, and exploratory study based on data from 2009 to 2012 obtained from the Breast Cancer Information System (SISMAMA) and the Unified Health System Information Data (DATASUS). The studied population consisted of women (n=31.195) with malignant breast cancer. The analysed variables were education level, race, nodule detection at the clinical examination or image studies, presence of palpable axillary lymph nodes, surgical approach, and tumor histological type and grade. Results. There was increasing detection of breast cancer cases in young women among the studied years. Young women had more palpable lymph nodes (OR 1.28, 95% CI: 1.18–1.39), ductal carcinoma as the most frequent histologic type (OR 1.36, 95% CI: 1.22 to 1.53), and grades II and III tumor (OR 16.01 , 95% CI: 13.30 to 19.28 ). The lesion detection by clinical examination was higher in women &lt;40 years (OR 1.34, 95% CI: 1.24 to 1.45). Conclusion. Although there are early detection measures related to breast cancer, they are not the usual practice of the young female public, suggesting the need for a review of existing public policies in the country.