Comparative Study of Breast Cancer in Women Under 40 Compared to Older Women: The Experience of the Mohammed VI Center

Context: Breast cancer in young women is relatively rare worldwide, with patients under the age of 35 accounting for only 2% to 25% of all women diagnosed with this cancer. The objective of this study is to describe the epidemiological, clinical and histological profile of breast cancer in patients under 40 years of age.

Methods: This is a comparative study between young and older patients at the Mohammed VI Center for Cancer Treatments. This study covered various aspects, including sociodemographic data and family history of cancer, gyneco-obstetrics, and circumstances of discovery of breast cancer, histopathological characteristics and molecular classification of breast cancer.

Results: Among the 305 patients treated, 64 were aged 40 or younger, or 20.98% of the total.

Breast cancer in our younger patients did not appear to differ significantly from that in older women, both in terms of sociodemographic factors and histopathological and molecular characteristics. The average age at first pregnancy was 23.85 years and the average parity was 1.58 children. 37.5% of young women were nulliparous. Among multiparous women, 95% breastfed their children.

The average age of menarche was 13.34 years in young patients compared to 13.30 years in older patients (p = 0.85). Among the 6 postmenopausal patients (9.3% young women), the average age of onset of menopause was 39.17 years. 59.4% of young women used oral contraceptives, compared to 60.2% of older women.

A family history of breast cancer was noted in 21.9% of young patients. The circumstances of discovery of breast cancer, most cases in both groups were identified by self-palpation or during a screening mammogram. The most common tumors were stage T2, involving lymph node invasion, and high-grade SBR II and III in 73.7% and 22.8% of cases, respectively. These were mainly invasive ductal carcinomas expressing hormonal receptors (ER and RP). About 30% were HER2+. No cases of bilateral cancer were observed in younger patients.

Conclusion: Breast cancer in young women is a significant problem in our study population and its incidence is increasing worldwide. The absence of a systematic screening program before the age of 40 may explain the aggressive behavior of tumors in this age group.

Breast cancer remains one of the main public health challenges worldwide, affecting millions of women each year. Although traditionally associated with older women, breast cancer in young women is a concerning reality that requires particular attention. While breast cancer in young women remains relatively rare globally, with only 2 to 25% of all cases affecting women under 35 [1-3], these rates are notably higher in North African countries, reaching 11% in Tunisia, 24% in Algeria, and 22% in Morocco, while they range between 2 and 4% in Western countries [4,5]. Young women, generally defined as those under 40 years old, represent a distinct population facing unique challenges in screening, diagnosis, treatment, and survival in the face of this disease [3,6-11].

Recent statistics underline the increasing importance of breast cancer in young women. According to the World Health Organization (WHO), breast cancer is the most common cancer in women worldwide, with nearly 2.3 million new cases diagnosed in 2020 [12]. Although breast cancer is less common in young women compared to older women, its prevalence is rising, and it is often diagnosed at an advanced stage in younger women, which can have significant implications for prognosis and quality of life [12-14].

Recent epidemiological studies have also highlighted distinct characteristics of breast cancer in young women, including a higher incidence of certain aggressive subtypes of breast cancer, such as triple-negative breast cancer, as well as specific challenges related to fertility, reproductive health, and psychosocial concerns [15-17].

Furthermore, young women may face unique barriers to early detection, including low awareness of breast cancer, difficulties accessing healthcare services, and delays in diagnosis due to the mistaken perception that breast cancer is a disease of older women [18-21].

The objective of this study is to analyze the epidemiological, clinical, and histological profile of breast cancer in young patients compared to older ones, treated at the Mohammed VI Center for Cancer Treatment. To highlight the critical importance of breast cancer in young women and to provide a context for exploring prevention and management strategies specifically tailored to this vulnerable population.

Patients and methods

This is a comparative analytical study carried out at the Mohammed VI Center for the treatment of cancers over two years, from January 2015 to December 2016. Patients with histologically confirmed breast cancer were divided into two groups in depending on their age: G1 for patients aged 40 or under, and G2 for those over 40.

The collection of variables was done consecutively and was completed using the medical records of the patients. We included all newly diagnosed patients who had not yet undergone cancer treatment, such as chemotherapy or radiotherapy, and who had no personal history of cancer.

Parameters analyzed include age at diagnosis, marital status, childbirth history, breastfeeding, menopausal status, family history of cancer and use of oral contraceptives, circumstances of the discovery of breast cancer, TNM stage and pathological characteristics (tumor location, SBR grade, and presence of vascular emboli).

For the immunohistochemical study, the tumors were classified into five molecular groups based on the expression of hormonal receptors (estrogen, progesterone), HER2 status and the Ki67 proliferation index:

• Luminal A (ER+ and/or PR+, HER2- and Ki-67 < 14%),
• Luminal B (ER+ and/or PR+, HER2+ and Ki-67 > 14%),
• Her2+ (ER-, PR-, HER2+),
• Basal-like or triple negative (ER-, PR-, HER2-)
• Unclassified (absence of overexpression of one of three molecules).

The analysis of variables was conducted using the R software. The chi-square test is performed, and a p < 0.05 is considered significant

During the study period, 305 patients were treated at the Mohammed VI center for the treatment of cancers. Among them, 64 were aged 40 or younger. We excluded patients who had already undergone cancer treatment. All patients agreed to participate in the study after being explained its significance and the importance of their contribution to breast cancer research in Morocco.

Sociodemographic parameters and family history of cancer

Regarding sociodemographic characteristics and family history of cancer, the results for the study population are presented in table 1.

We observe that 20.98% of breast cancers were diagnosed in women under the age of 40, with an average age at diagnosis of 35.86 years. The majority of these young women were either married (60.9%) or divorced (12.5%), together accounting for 73.4% of cases, while single women accounted for only 26.6%.

Among young patients, 21.9% had a family history of breast cancer, including 7.81% first degree and 7.81% second degree. Family history of other types of cancer was observed in 29.7% of patients, with 9.37% first degree and 14.06% second degree. In comparison, in the group of older patients, a family history of breast cancer was observed in 19.9% of cases, including 10.7% first degree and 4.14% second degree. Family history of other types of cancer was noted in 24.5% of cases, with 11.61% first degree and 6.22% second degree.

Gyneco-obstetric history

Antecedent findings gyneco-obstetrics in the study population are presented in table 2.

The average age of first pregnancy was similar between the two groups, with 23.85 years for the G1 group and 23,69 years for the G2 group, with no significant difference (p = 0.88). However, parity was on average 1.58 children for the G1 group and 2.80 children for the G2 group, with a significant difference (p =0.0001). 32.8% of young women had 1 to 2 children compared to 23.7% of older women, while older women had more than two children. In addition, 37.5% of young women were nulliparous compared to 24.1% of older women, with a significant difference (p = 0.02).

Regarding breastfeeding, among multiparous women, 95% of young women had breastfed their children, which was similar to 96.7% of older women, with no significant difference (p = 0.48). However, the cumulative average duration of breastfeeding was shorter in younger women (35 months) than in older women (50.85 months), with a significant difference (p = 0.03).

The age of menarche was similar between the two groups, with 13.34 ± 1.45 years in young patients and 13.30 ± 1.75 years in older patients, with no significant difference (p = 0.85). Menopausal status was mainly pre-menopause in young women (89.1%) and menopause in 9.3% of them, with a mean age of onset of menopause of 39.17 ± 0.75.

The use of oral contraceptives was similar between the two groups (59.4% for group G1 and 60.2% for group G2, p = 0.50). However, 60,2% of older patients had taken oral contraceptives for more than 5 years compared to 39,5% of younger patients, with a significant difference (p = 0.001). The average duration of oral contraceptive use was also longer in older women (9.28 years) than in younger women (5.18 years), with a significant difference (p = 0.001).

Circumstances of discovery of breast cancer

Results concerning the circumstances of diagnosis of breast cancer in the study population are presented in table 3.

Self-palpation was the main method of diagnosis, both in young women (42.2%) and in older women (41.9%). Screening mammography was less common, accounting for 7.8% of cases in younger women and 9.5% in older women. Additionally, 4 young patients (6.2%) were detected during a screening campaign, while16 elderly patients (6.6%). No significant differences were recorded under these discovery circumstances.

Histopathological features

The histopathological characteristics of breast tumors are summarized in table 4.

Tumors were similarly distributed between the left breast (48.4%) and the right breast (51.6%) in young patients. As for the bilateral form of breast cancer, it was not found in the young people in our series compared to 8 (3.3%) elderly patients.

Histologically, infiltrating ductal carcinoma was the predominant type, with 75% of cases for group G1 and 78.4% for group G2. The tumors were classified according to their SBR grade: in the G1 group, 2 cases (3.5%) were of SBR grade I, 42 cases (73.7%) were of SBR grade II and 13 cases (22.8 %) were SBR grade III. In the G2 group, we observed 17 cases (8,1%) of SBR grade I, 141 cases (66,8%) of SBR grade II and 53 cases (25.1%). of SBR grade III, but there was no significant difference between the groups. Vascular emboli were more common in younger patients (51.5%) than in older patients (36.6%), although the difference was not significant.

According to the TNM classification, tumors classified as T2 were the most frequent in both groups, representing 44.1% in the G1 group and 52.9% in the G2 group. As for the lymph node status, it was N0 in 12 cases (40%) of the G1 group and 46 cases (35.4%) of the G2 group. N1 status was observed in 7 cases (23.3%) of the G1 group and 35 cases (26.9%) of the G2 group, while N2 was noted in 8 cases (26.7%) of the G1 group and 34 cases (26.2%) of group G2. At the end of the extension assessment, it was noted that 16 patients in group G1 presented metastases, while 79 patients in group G2. No significant differences were noted.

Molecular characteristics and classification of breast cancer

Table 5 presents the distribution of patients according to molecular classification.

Analysis of the status of hormonal receptors and the search for overexpression of the HER2 protein made it possible to identify, in the G1 group, 38 cases of ER+ tumors (88.4%), 35 cases of RP+ tumors (81.4 %) and 10 HER2+ (29.4%). In the G2 group, 148 cases (80.4%) were ER+ tumors, 128 cases (69.9%) were RP+ tumors and 50 cases (29.9%) presented overexpression of HER 2, with no difference. significant between the two groups.

According to the molecular classification, for the group of young women, the tumors were mainly of Luminal A phenotype in 53.5% of cases, of Luminal B phenotype in 7% of cases and of triple negative basal type in 9.3% of cases. . No cases of HER2 type (non-Luminal) were found. For the group of elderly women, the tumors were of Luminal A phenotype in 52.2% of cases, of Luminal B phenotype in 7.1% of cases, of HER2 phenotype in 4.3% of cases and the basal type in 14.1% of cases.

Breast cancer in women under 40 is common in our study population, representing 20.98% of cases, which is approximately one in five women. This prevalence is notably higher than that observed in the United States (5 to 7%) [22,23] and in Europe [24,25]. The average age of cancer onset in our patients is 35.86 years, with the youngest patient diagnosed at the age of 24. Cases of breast cancer in women as young as 14 years old have been reported in the literature [26].

Compared to older women, breast cancer in young women presents a poorer prognosis and higher aggressiveness. Survival rates are generally lower in younger women than in older ones [23]. This observation underscores the importance of early detection and appropriate management of breast cancer in young women to improve clinical outcomes and survival.

Several factors may contribute to the increased aggressiveness of breast cancer in young women, including distinct biological characteristics of tumors, a higher likelihood of genetic mutation, faster tumor growth, and environmental or behavioral factors specific to this age group. A better understanding of these factors can guide the development of more effective prevention and management strategies for this vulnerable population [27,28].

Recent studies have also highlighted racial and ethnic disparities in the incidence and outcomes of breast cancer in young women, emphasizing the importance of an individualized approach that considers sociodemographic factors in disease management. By integrating this knowledge into breast cancer screening, diagnosis, and treatment programs for young women in Morocco, it is possible to improve clinical outcomes, reduce health disparities, and save lives [29-33].

In our series, most women with breast cancer are married women, accounting for 60.9% of our study population. This observation contradicts the findings [34,35], who suggested that unmarried women were more likely to develop breast cancer than married ones

This difference may be influenced by several socio-cultural and demographic factors specific to the Moroccan context. For example, marriage may be associated with different health practices, such as better attention to preventive healthcare and more proactive medical care. Additionally, married women may benefit from increased social and family support, which can have a positive impact on their physical and emotional well-being.

However, it is important to note that breast cancer risk factors are multifactorial and complex, and they may vary depending on different sociocultural contexts. By integrating this data into the design and implementation of breast cancer prevention programs, it is possible to develop more effective strategies to reduce the incidence of the disease and improve clinical outcomes for all women in Morocco, whether married or unmarried.

In our series, several factors may contribute to the early onset of breast cancer in young women. Among these factors, family history is an important risk factor for breast cancer development. The rates of family history of breast cancer and other types of cancer are 21.9% and 29.7%, respectively. This notion of familial predisposition has also been found in 21% of Tunisian patients [11].

However, these rates are significantly higher than those reported in other populations. For example, a study in Korea reported family history rates of breast cancer of 8.7% and 8.5%, respectively [36], while a study in the United States reported similar figures [37]. This disparity can be partly explained by the high number of consanguineous marriages, which are widespread in North Africa.

Indeed, among our patients with a family history of breast cancer, first-degree relatedness was present in 35.7% of cases, which is consistent with an epidemiological study demonstrating that a first-degree family history increases the risk of developing breast cancer by 80% [38]. Thus, a woman with a first-degree relative affected by breast cancer is approximately twice as likely to develop the disease herself [39-41].

These findings underscore the importance of evaluating family history in assessing individual breast cancer risk in young women. Special attention should be paid to the collection and analysis of family history during medical consultations, especially in regions where consanguinetaleous marriages are common. This could allow for early identification of women at increased risk of breast cancer and facilitate the implementation of screening and prevention measures tailored to their specific situation.

Hormonal factors play a crucial role in the risk of breast cancer development, as it is a hormone-dependent pathology, mainly influenced by estrogens. The age at which puberty occurs is of great importance, as the onset of the first menstrual period before the age of 12 increases the risk of breast cancer in adulthood by exposing women to higher levels of estrogen over a prolonged period. Therefore, each additional year of age at the time of the first menstruation reduces the risk of breast cancer by 5% [42-46]. Conversely, the onset of the first menstruation after the age of 14 seems to have a protective effect [47]. In our series, the average age at which menstruation first occurred is 13.34 ± 1.45 years, and 31.2% of young women experienced menarche before the age of 12.

Late menopause increases the risk of breast cancer due to prolonged estrogen production, especially during the menopausal transition period (peri-menopause). In our study, over 89% of young women had not yet reached menopause. Combined with the early age of their first periods (< 12 years), this results in prolonged exposure to estrogen. Several studies have confirmed that each year increases the risk of breast cancer by 3% [48].

Furthermore, prolonged use of oral contraceptives containing estrogen and progestin increases the risk in young women. In our series, 39.5% of young women had taken oral contraceptives for more than 5 years during their lifetime, while this figure rose to 68.3% among older women. A meta-analysis of 54 studies reveals that oral contraceptive use is associated with a relative risk of developing breast cancer of 1.24, although this risk decreases in the ten years following cessation (RR: 1.01) [49].

These findings emphasize the importance of considering hormonal factors in assessing the individual risk of breast cancer in young women. Special attention should be paid to menstrual history and the use of hormonal contraceptives when assessing the overall risk of breast cancer in young women, in order to implement prevention and management strategies tailored to their specific profile.

Parity and breastfeeding are widely recognized as the most important protective factors against breast cancer. The protective effect of these factors increases with the number of children and early age of first pregnancy [50-52]. In our study, over 37% of young women were nulliparous, 17.5% had their first pregnancy after the age of 30, and 22.5% had it before the age of 20. Thus, a first pregnancy before the age of 30 reduces the risk of breast cancer by 25% compared to a woman without children, and a first pregnancy before the age of 20 decreases the risk by 30% compared to a woman who had her first pregnancy after 35 [53].

Breastfeeding as a protective factor is subject to discussion [54,55]. Nevertheless, breastfeeding appears to reduce the risk by approximately 4% when prolonged for more than 12 months. According to Robles-Castillo, et al. [56] breastfeeding reduces the risk of invasive breast cancer in women under 40, even in those carrying the BRCA1 gene, especially with prolonged breastfeeding [56,57]. These results seem to contradict those of our study.

The increase in the overall incidence rate of breast cancer among young Moroccan women appears to mainly result from the rise in the incidence of tumors expressing positive hormone receptors. Hormonal factors may be responsible for this surge in breast cancer, which predominantly affects women and young individuals. Our study suggests that nulliparity, early age of menarche, as well as family history of breast cancer, are associated with an accumulated risk of developing hormone-sensitive tumors. The severity of the disease is linked to a higher prevalence of moderately differentiated tumors (grade II), the presence of vascular emboli, and lymph node involvement with metastasis formation. The absence of systematic screening programs for young women explains the aggressive nature of tumors in this age group.

These findings underscore the urgent need for preventive action and increased awareness of breast cancer among young women in Morocco. Early screening programs, specifically targeting this at-risk population, are necessary to detect tumors at an early stage when treatment options are most effective. Additionally, initiatives aimed at promoting healthy lifestyles, encouraging motherhood at an appropriate age, and raising awareness of family history of breast cancer can help reduce the incidence of this disease.

Furthermore, a better understanding of the underlying molecular mechanisms of breast cancer in young Moroccan women is necessary to guide the development of targeted and personalized therapies. Precise characterization of breast cancer subtypes and identification of specific risk factors in this population can guide prevention and treatment strategies to improve clinical outcomes and survival.

Finally, multidisciplinary collaboration among healthcare professionals, researchers, policymakers, and civil society organizations is essential to implement integrated and effective initiatives to combat breast cancer among young women in Morocco, providing comprehensive support from early screening to treatment and post-treatment management.

What is known about this subject?

Breast cancer remains the most common form of cancer among women globally, accounting for approximately 25% of female cancer cases, with a higher prevalence in developed countries.

This disease is complex and multifactorial, involving various identified risk factors, such as age (the risk of breast cancer increases considerably from the age of 40), family factors, particularly of the first degree, as well as gynecological factors. . -obstetric (such as early puberty, late menopause, or a first pregnancy after age 30), and lifestyle factors, such as physical activity.

Breast cancer in young women is distinguished by its particular epidemiological, diagnostic and prognostic characteristics. It is often associated with a greater genetic predisposition and is correlated with reduced survival as well as higher recurrence rates compared to older women.

What's new in your study?

Our study highlights a high incidence of breast cancer among young Moroccan patients. In this context, it is characterized by a diagnostic delay frequently associated with an advanced stage at the time of diagnosis. The biological characteristics of tumors are often more aggressive, including high histological grade, absence of hormonal receptors, as well as a greater proportion of triple negative tumors, considerably limiting therapeutic possibilities.

Our results led us to formulate recommendations aimed at improving the management of breast cancer in young women. We emphasize the need to raise awareness among medical teams and the population of the importance of annual clinical breast examinations in women at risk before the age of 40, as well as the prescription of a mammogram. Screening every two years in young women. Therapeutic management adapted according to various prognostic factors is also essential, as is local monitoring of the disease.

Finally, consider our emphasis that age should not be the only determining factor in treatment decisions. It is crucial to take into account the multiple aspects of the patient's physical and mental health, as well as her medical, social and family environment for comprehensive care [58-84].

Conflicts of Interest

The authors declare no conflict of interest.

Author contributions

All authors contributed to the conception, production, and development of this work. They also declare that they have read and approved the final version of the manuscript.

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