Mapping a Decade of Breast Cancer Research in Morocco: A Bibliometric Analysis (2010–2022)

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

Introduction Breast cancer is the most common malignancy affecting women under the age of 35 and young age at diagnosis is associated with a poor prognosis. Previous studies have shown that these patients have adverse tumour biology including high grade morphology, lymph node involvement and lack of hormone receptor expression. The aim of this study was to assess the outcomes and risk factors associated with the different subtypes of breast cancer as defined by receptor status in a cohort of young patients in a central London cancer centre. Methods Women diagnosed with breast cancer at the age of 35 or younger between 1st January 2010 and 1st June 2020, at Guys and St Thomas’ NHS Foundation Trust (GSTT) were identified from the GSTT Breast Cancer Clinical Database. Data on patient demographics, histopathology, treatment, family history of breast or ovarian cancer, recent use of oral contraceptive pill (OCP) and outcome were collected from electronic hospital records. Risk factor data was analysed using chi-squared (χ2) statistical analysis; survival data (Overall survival (OS) and recurrence free survival (RFS)) was assessed using cox-regression analysis and formulation of Kaplan-Meier curves. Results We identified 119 patients with a median age of 32.5 years (range 22-35 years). Four were diagnosed with in situ carcinoma (3 DCIS, 1 LCIS) and the remainder were invasive cancers. Of the invasive cancers, 54% (n= 62) were ER+HER2-, 23% (n=26) ER-HER2-, 19% (n=22) ER+HER2+ and 4% (n=5) ER-HER2+. The majority of patients presented with stage 1 or 2 disease and a small number presented with metastatic disease, irrespective of subtype. Approximately 23% (n= 28) of patients had taken the OCP and 15% (n=18) of patients were pregnant or breast feeding at the time of diagnosis, with no variation by subtype. ER+HER2+ patients were less likely to have had children (p=0.0008). ER+HER2- patients were more likely than ER-HER2- patients to have a family history of breast cancer (P=0.03), but were less likely to be referred for genetic testing (52% (n=38) vs 81% (n=21)). 11.8% (n=14) were found to have a germline mutation, two occurred with in situ cancer (BRCA2 in the case of LCIS and TP53 in a case of ER+HER2+ DCIS). Of the ER+HER2- cases that underwent genetic testing 12.5% (n=4) had a germline mutation (2 BRCA2, 1 PALB2, 1 CHEK2) and 38% (n=8) of the ER-HER2-subgroup (6 BRCA1, 2 BRCA2). With a median follow up of 29 months (range 3.1 to 103.3 months), 23% of ER-HER2-, 10% of ER+HER2- and no HER2+ cases had developed a recurrence (loco-regional or distant). 5-year RFS in ER+HER2- was 79.5% vs. 61.9% in ER-HER2- (HR 2.96, 95%CI 0.95-9.20; p=0.061). Of the ER+HER2- patients that recurred, 83% (n=5) had full ovarian function suppression (OFS) with Goserelin. Mean survival was 36.4 months; 12 out of 115 patients died, the 5-year OS across all subgroups was 76.7%. ER-HER2- patients were more likely to have died (27% (n=7) (HR 5.9 95%CI 1.69-20.46; p=0.005), with a 5-year OS of only 47%. Only 6% (n=4) of ER+HER2- patients died, they had a 5-year OS of 89.3%. Only 5% (n=1) of ER+HER2+ patients died (HR 1.47 95%CI 0.16-13.80; p=0.733) with a 5-year OS of 75%. Conclusions Despite optimum treatment, 23% of women under 35 with ER-HER2- breast cancer still died from their disease. In addition, even with this relatively short follow up, there is a subgroup of ER+HER2- patients who presented with a low nodal burden, were treated with full OFS and still recurred. This group of patients would benefit from somatic molecular testing to identify potential treatment targets. The majority of HER2+ patients in this cohort also had ER+ disease which is similar to previous reports of HER2+ breast cancer in young women. However contrary to that report, HER2+ positive patients in our study had a low risk of recurrence, this is likely due to the widespread use of targeted anti-HER2 therapy. Citation Format: Joanna Dodkins, Elizabeth Harvey-Jones, Sameer Sengupta, Jasmine Timbres, Angela Swampillai, Elinor Sawyer. Outcomes and risk factors associated with breast cancer in women aged 35 and under: Single centre retrospective analysis [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 PS7-83.

Mammography for Older Women?

Breast cancer is one of the main causes of women’s death. Breast cancer is the most common cancer in women over the world. Various studies have reported different incidence of breast cancer in women. However, we found no comprehensive study that showed the results of these studies in general, so the present study was conducted aimed to determine the prevalence of breast cancer in Iranian women in a systematic review and meta-analysis study. In this review study, with searching national and international databases of SID, MagIran, IranMedex, IranDoc, Google Scholar, Cochrane, Embase, ScienceDirect, Scopus, PubMed and Web of Science, the data were extracted between 1965 and September 2019. The random effects model was used for analysis, and heterogeneity of studies was investigated using I2 index. The data were analyzed using software Comprehensive Meta-Analysis (version 2). The prevalence of breast cancer in Iranian women in 24 papers with a sample size of 39,596 patients was 23.6% (95% CI: 15.3–34.7%). A significant difference was found in the prevalence of breast cancer in Iranian women regarding heterogeneity based on meta-regression, year of study and sample size (P < 0.005). The study results show that the prevalence of breast cancer in Iranian women is high. Hence, appropriate solutions should be applied to improve the aforementioned situation, find causes and monitor by providing feedback to hospitals at all levels.

Mortality rates from breast cancer in young women have fallen considerably in high-income countries but continue to rise in low-income countries such as Morocco. Young women with breast cancer face unique challenges due to the aggressive nature of the disease, the presence of aggressive subtypes (e.g., triple-negative, HER2-positive, and luminal B), and limited access to timely diagnosis and treatment. In addition, genetic factors play crucial roles in patient prognosis and response to treatment. The molecular landscape of breast cancer in young women has important implications for personalized medicine, such as the use of targeted therapies, namely poly (ADP-ribose) polymerase (PARP) inhibitors, which are particularly effective in patients with BRCA gene mutations. However, research into the genetic landscape of breast cancer in young women from low-income regions is limited, and the potential of personalized medicine to improve outcomes remains underexplored. This study aims to analyze the genetic landscape of breast cancer in young Moroccan women, with a focus on genetic alterations beyond the BRCA1 and BRCA2 genes. By expanding the panel of genes, we hope to identify other genetic variants that may influence the diagnosis, treatment, and follow-up of this high-risk population. Methods A retrospective study was conducted on 60 young women who were diagnosed with breast cancer between 2019 and 2024 at Hassan II University Hospital, Fez, Morocco. Genetic analysis was performed via next-generation sequencing (NGS) technology, specifically the Ion S5 sequencer and a custom-designed gene panel targeting 28 key genes associated with breast cancer and hereditary cancer syndromes. For statistical analysis, descriptive statistics were calculated for clinical variables (e.g., age, grades, molecular subtypes, genetic mutations). The correlation between genetic mutations and clinical outcomes was assessed using chi-square tests. All statistical analyses were performed using SPSS software. A significant level of p < 0.05 was used for all tests. Results The cohort had a mean age of 34.6 years, with 36.7% reporting a family history of cancer. DNA sequencing of the 60 patients yielded 15 pathogenic variants and 3 likely pathogenic variants; the genes involved being BRCA1, BRCA2, and ATM for the pathogenic variants, whereas for the likely pathogenic variants, the genes involved were MUTYH and APC, which suggests the presence of other potential genetic risk factors other than the BRCA1 and BRCA2 genes. Furthermore, the BRCA1 gene was mutated in 45% of patients with triple-negative breast cancer, highlighting the important role of genetic testing in identifying high-risk patients, which should greatly improve the management and treatment of the disease. Conclusion This study highlights the importance of genetic testing for personalized treatment of young breast cancer patients. Firstly, these results will help us to improve outcomes for young women with aggressive subtypes in low-income countries through the adaptation of targeted therapies such as PARP inhibitors. Secondly, this study will help us to identify at-risk family members, so that we can detect breast cancer at an early stage and adapt care accordingly. And finally, this study has allowed us to identify genes of interest other than the two BRCA1 and BRCA2 genes, demonstrating the diversity in this population.

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

Background: Though breast cancer is the most commonly diagnosed cancer and the leading cause of cancer death in women worldwide, relatively little is understood about the differences in prevalence and biology between various populations. For example, breast cancer is far less common in Asia than in North America, and the biology of breast cancer is likely different between these groups as well. There is some limited data to suggest that Asian breast cancer patients may have 35-40% rate of HER2+ breast cancer [1,2], as compared to 15-23% within the general American population [3,4]. Methods: To further examine this possibility, we reviewed our data at the Harris Health Systems' Smith Clinic in Houston, Texas from September 2010 through September 2014 to further characterize the Vietnamese breast cancer patients seen during that time. Using Fisher's Exact Test, we compared our subset of Vietnamese breast cancer patients with the publicly available SEER data from 2010[4]. Results: Among the Vietnamese patients from the Smith Clinic, we found that out of 33 patients with invasive breast cancer, 15 (45%) had HER2+ breast cancer. Interestingly, 64% of the HER2+ cohort was post-menopausal, and 50% of the post-menopausal women had HER2+ breast cancer. Compared with the 2010 SEER data that encompasses 28% of all US breast cancer patients diagnosed that year, regardless of race, the Smith Clinic Vietnamese cohort had a statistically significant higher rate of HER2+ breast cancer, with an odds ratio of 4.7 (45% vs. 15%, p &amp;lt;0.001). Among the women greater than 50 years old in both groups, the Vietnamese women had a higher rate of HER2+ breast cancer than the same age group in the SEER data group (odds ratio 7.0, p &amp;lt;0.001). Conclusion: The patterns observed in this small Vietnamese cohort, and others, do not mirror those seen in the general, multi-racial American breast cancer population. The rate of HER2+ breast cancer in the Smith Clinic Vietnamese group is twice that of the general American population. Other, larger studies have supported the findings of this small group, including a 242-patient study in Vietnam which demonstrated a 41% rate of HER2+ breast cancer; 55% of post-menopausal women had HER2 mutated tumors in this group [1]. Generally, other studies have associated older age and post-menopausal status with a lower rate of HER2+ breast cancer [5,6], but the opposite is true in these Vietnamese women. This unique pattern of breast cancer in Vietnamese women may suggest an underlying genetic or environmental driver, similar to the higher rate of triple negative breast cancer in BRCA1 carriers, or HER2+ breast cancer in women with p53 mutations. We plan to conduct further epidemiologic and genetic research in a larger cohort of Vietnamese breast cancer patients to determine whether an underlying germline genetic mutation or environmental exposure may explain this unusual pattern of breast cancer.

BackgroundAlthough several studies have evaluated the risk of gynecological cancers in women with polycystic ovary syndrome (PCOS), there are controversies regarding it.ObjectiveThis study aimed to investigate the association of PCOS with endometrial, ovarian, and breast cancers.Materials and MethodsPubMed, Scopus, Web of Science, and Google Scholar databases based on MESH terms using the combination of the appropriate keywords were searched to retrieve observational studies on endometrial, ovarian, and breast cancers in PCOS women, published from inception to April 2020. This meta-analysis was performed to determine the pooled odds ratio (OR) of these cancers in women with PCOS. Publication bias was assessed by using Begg's test.ResultsOf 1347 records retrieved by searching the databases, a total of 14 articles were included in the study. Overall, the pooled OR of the composite outcome, including endometrial, ovarian, and breast cancers in women with PCOS was higher than that of women with no PCOS (pooled OR: 1.4, 95% CI: 1.0-1.9). The pooled OR of endometrial (pooled OR: 2.2, 95% CI: 1.03-4.7) and ovarian (pooled OR: 1.3, 95% CI: 1.0-1.8) cancers in women with PCOS was higher than the control group, whereas the pooled OR of breast cancer was not significantly higher than that of the control group.ConclusionThis meta-analysis indicated an increased risk of endometrial and ovarian cancers in women with PCOS.

Breast cancer chemoprevention: little progress in practice?

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.

Age-Specific Analyses of Breast Cancer Versus Heart Disease Mortality in Women

A discussion of the management of breast cancer in young women is presented. The rate of growth of breast cancer is not influenced by the age of the patient, as reflected in the fact that the expected survival rate for women of all ages is 50% at 5 years. Although it has been reported that the time lapse for the recurrence of cancer was less for younger women with affected nodes than older women, the literature is not in agreement on this point. The prognosis for women in whom cancer is diagnosed in late pregnancy, or during lactation, is usually grave. Pregnancy subsequent to treatment of breast cancer poses problems, though it has been reported that the survival rate of pregnant women following mastectomy is improved. It is recommended that a young, nulliparous woman should not be discouraged from having children after the removal of a small localized tumor. Permanent sterilization may be preferable to oral contraception for women who probably should not have another pregnancy. In the United Kingdom, the mortality rate from breast cancer in women aged 35-44 has increased by almost 20% from 1968 to 1972. A marked reduction in the early recurrence of breast cancer in premenopausal women with nodal deposits has been reported as a result of adjuvant systemic chemotherapy.

Evaluation of the insulin-like growth factors (IGF) IGF-I and IGF binding protein 3 in patients at high risk for breast cancer

10524 Background: To examine trends in postmenopausal breast cancer and mammogram utilization in Asian and White women in the United States. Methods: Data on postmenopausal breast cancer was obtained from the United States Cancer Statistics Public Use Database from 2001 and 2018. Rates of mammogram screening for women ages 18 and older were evaluated using the Behavioral Risk Factor Surveillance System (BRFSS) between 2000 and 2018. Obesity rates for women ages 18 and older were extracted from BRFSS between 2001 and 2016. SEER*Stat 8.3.8 and Joinpoint regression program 4.8.0.1 were used to calculate incidence trends. Breast cancer incidence and trends were described using average annual percent change (AAPC). Mammogram screening trends were described using average biennial percent change (ABPC). Obesity trends were described using AAPC. Age groups were divided into five-year or ten-year intervals. Results: The incidence of metastatic postmenopausal breast cancer in women was 19.48/100,000 in 2018 has increased by 1.03% annually over the past eighteen years (p = 0.000). In 2018, the incidence of advanced-stage breast cancer in Asian and White women was 12.17/100,000 and 19.17/100,000 respectively. Over time, the incidence of advanced-stage breast cancer has increased in Asian women by 2.19% annually (p = 0.000), but remained stable in White women. In a subset analysis of early-stage breast cancer, there was no difference in both Asian and White women. Using the BRFSS data, we evaluated the utilization of mammograms. In the overall population, 20.92% were newer screened and this was higher in Asian women at 40.99% compared to 18.17% in White women in the year 2018. Given the potential association of obesity and breast cancer, we then evaluated the rate of obesity in these two groups. Our data showed that the incidence of obesity was low in Asian women at 12.8% compared to 28.13% in White women. Conclusions: There is an increased incidence of advanced-stage breast cancer in Asian women in the U.S. Although Asian women are less obese but they are also less likely to undergo screening compared to White women.

Sleep-disordered breathing (SDB) has been related to a higher risk of breast cancer whereas the results of previous studies are inconsistent. We, therefore, performed a meta-analysis to evaluate the association between SDB and subsequent risk of breast cancer in women. Cohort studies that investigated the temporal relationship between SDB and breast cancer incidence were obtained via search of PubMed, Embase and Web of Science from inception to 30 January 2021. Only studies with multivariate analyses were included. A fixed or a randomised effect model was applied according to the heterogeneity. Eight cohort studies with 1398113 women were included. Pooled results with a randomised-effect model showed that compared with women without SDB at baseline, women with SDB had a significantly increased risk of breast cancer (risk ratio [RR]: 1.36, 95% confidence interval [CI]: 1.08 to 1.71, P=.01) with significant heterogeneity (P for Cochrane's Q test<.001, I2 =95%). Subgroup analyses showed that SDB seemed to confer a more remarkably increased risk of breast cancer in elderly women (RR: 3.00, 95% CI: 1.33 to 6.76, P=.008) than that in non-elderly women (RR: 1.15, 95% CI: 1.02 to 1.29, P=.02; P for subgroup difference=.04). However, the association was not significantly affected by country of the study, study design, diagnostic strategy for SDB or adjustment of obesity (P for subgroup analyses all>.05). SDB may be an independent risk factor for breast cancer in women, particularly in elderly females.