Summary
Objectives:
This study aimed to assess the incidence of breast cancer in young women over a ten-year period and examine its association with clinical characteristics, risk factors, treatment modalities, and survival outcomes.
Methods:
A retrospective analysis of the Breast Cancer Registry at our institution was conducted. Of the 2,238 women diagnosed with breast cancer between 2012 and 2021, 535 (23.9%) were aged 40 years or younger at the time of diagnosis. Cases with missing data for independent variables were excluded from the respective analyses.
Results:
The mean age at diagnosis was 34.5 years (range: 15–40). The most common clinical stage at presentation was IIB (25.2%), followed by IIA (24.4%), while 7.6% of patients presented with metastatic disease. Invasive ductal carcinoma was the predominant histological type (88.8%), and 57.4% of tumours were high grade. Triple-negative breast cancer accounted for 27.0% of cases, and 18.4% were ERBB2-enriched. Bilateral disease was observed in 2.5% of cases, and 7.5% were diagnosed during pregnancy. A family history of breast cancer was reported in 23.6%. Genetic testing was performed in 10.9% of patients, with BRCA1 mutations being the most frequently identified (12.1%). Modified radical mastectomy was performed in 38.2% of patients, and 8.2% underwent reconstructive surgery. Neoadjuvant chemotherapy was administered in 49.9% of cases, and 68.2% received adjuvant radiotherapy. The five-year overall survival rate was 93.9%, with 12 patients (2.4%) experiencing distant and one (0.2%) experiencing local recurrence within five years.
Conclusion:
Young women with breast cancer in resource-limited settings demonstrate distinct sociodemographic and clinicopathological characteristics, underscoring the importance of early detection strategies and personalised treatment approaches.
Keywords: Breast Neoplasms, Risk Factors, Epidemiology, Survival
Advances in Knowledge
Young women with breast cancer are more likely than their older counterparts to present with aggressive tumour subtypes and more advanced stages of disease at diagnosis.
This patient cohort is at a higher risk of disease recurrence and therefore requires prolonged clinical surveillance.
Breast cancer in young women represents an independent indication for genetic testing, with significantly higher rates of mutation positivity compared to older populations.
Application to Patient Care:
Young women with breast cancer exhibit distinct sociodemographic and clinicopathological profiles, emphasising the importance of early detection and individualised treatment strategies.
Optimal care for this population necessitates the involvement of a multidisciplinary team, addressing long-term management, fertility preservation, genetic counselling, physiotherapy, occupational therapy, nutrition, and psychosocial support.
Genetic testing plays a critical role in informing adjuvant systemic therapy, decision-making regarding prophylactic surgery versus high-risk surveillance, and the screening of asymptomatic family members.
1. Introduction
Breast cancer (BC) stands out as the predominant malignant tumour diagnosed among women.1 The worldwide impact of BC on women, as gauged by its incidence, mortality rates, and economic ramifications, is significant and escalating. In a recently published cancer statistics data from Pakistan, BC was reported to be the most prevalent cancer in all age group and sexes constituting 22% of total cancer population.2 BC ranks as the most prevalent cancer type among adolescents and young adults aged 15–39 years at the time of diagnosis, constituting 30% of cancers diagnosed in women within this age group and as per Surveillance, Epidemiology, and End Results (SEER) data, 5.6% of all cases of invasive BC manifest in adolescent and young women.3
Recent research indicates an upward trajectory in the incidence of BC among young women and in comparison to older women, young women have a higher propensity to develop BC with more aggressive biological characteristics.4,5 These include larger tumour size, advanced tumour stage, negativity for hormone receptors (oestrogen receptor [ER] and progesterone receptor [PR]), and overexpression of the human epidermal growth factor receptor 2 (ERBB2). These factors collectively contribute to a less favourable prognosis among young female BC patients.6,7 Adolescent and young women face a significantly elevated risk of mortality, with a 39% higher likelihood compared to their older counterparts.8 Additionally, after undergoing treatment, young women with BC encounter a range of challenges, including early onset of amenorrhea, fertility issues, social and psychological concerns, and a significantly elevated genetic predisposition compared to older individuals.9 Furthermore, adolescent and young women tend to experience a greater incidence of therapy-related side effects and encounter a myriad of psychosocial challenges following their diagnosis.10 These observations underscore the unique and complex nature of BC in young women, necessitating tailored approaches to both treatment and supportive care.
Numerous obstacles impede BC patients in lower-middle-income countries, which may contribute to the lower incidence and higher mortality rates compared to high-income countries.11 These barriers encompass various aspects, including limited BC awareness stemming from inadequate health education and awareness programs, absence of screening initiatives due to insufficient governmental support and financial resources, societal hindrances to early diagnosis and treatment owing to the marginalized status of women's health issues in predominantly patriarchal developing societies, concerns about job loss and cultural taboos surrounding cancer, as well as misconceptions regarding treatment outcomes.11,12 Although no randomized trials have demonstrated a direct impact on breast cancer mortality, targeted screening for select high-risk young women may offer potential benefits. Current recommendations are based on expert consensus.13 Additionally, challenges include the absence of standardized treatment protocols, resulting in diverse clinical practices, disparities in healthcare standards and infrastructure, and inadequate follow-up data coupled with a lack of mortality statistics.
To date, there has been a notable absence of published studies from Pakistan focusing on BC in young women. The primary objective of the current study is to meticulously examine the clinical and pathological profiles, as well as treatment outcomes and survival among BC patients under the age of 40.14
2. Methods
This descriptive, cross-sectional study involved meticulously gathering and analysing retrospective data from the electronic medical records of BC patients treated at the Aga Khan University Hospital (AKUH), Karachi, Pakistan. The study was conducted during June 2024 and included a cohort of 535 patients who were diagnosed with BC between the period of January 2012 and December 2021 with follow-up till December 2021.
Throughout the study, an extensive examination was conducted, encompassing various facets of patient characteristics and disease biology. This included a comprehensive review of demographic information, familial medical history, pathological features of the tumours, types of surgical interventions performed, the presence of metastatic disease, and recurrence rates. The collected data were meticulously analysed allowing for a detailed understanding of the observed trends and outcomes within the patient population under investigation. Continuous variables such as age were reported as mean ± standard deviation. Categorical variables were reported as proportions and percentages. Kaplan-Meier survival analysis was performed to evaluate 5-year overall survival of the patients and assess its variation by age and stage. Overall survival was calculated from the date of diagnosis to the date of death due to any cause and those alive were censored at their last follow up. Hence, it is a 5-year analysis and follow up till December 2021 only. All the statistics was performed using Statistical Package for the Social Sciences (SPSS), Version 23 (IBM Corp., Armonk, New York, USA).
We enrolled exclusively female patients diagnosed with BC at the age of 40 or younger at AKUH, Karachi between January 2012 and December 2021 irrespective of their nationality, religion, or racial and ethnic backgrounds. Conversely, male patients and those diagnosed with BC above the age of 40 were excluded from the study sample.
The study received ethical approval from the Ethical Review Committee (ERC) at The Aga Khan University Hospital (AKUH) Karachi, Pakistan, before its commencement.
3. Results
The median follow-up duration was 60 months. Of the 2,238 women diagnosed with BC at our centre between 2012 and 2021, 535 (23.9%) were aged under 40 years at the time of diagnosis. The mean age of this cohort was 34.5 years (range: 15–40 years). At presentation, clinical staging revealed that 25.2% of patients had stage IIB disease, followed by 24.4% with stage IIA, while 7.6% presented with metastatic disease. Bilateral BC was diagnosed in 2.5% of patients. A positive family history was reported in 23.6% of the cohort, and 7.5% were diagnosed with pregnancy-associated BC (i.e. BC diagnosed during pregnancy or within one year postpartum). Tumour biology data were available for 348 patients; among these, 44.3% were hormone receptor-positive and ERBB2-negative, 27.0% were triple-negative, and 57.4% had high-grade tumour biology. Histologically, invasive ductal carcinoma was the predominant subtype, identified in 88.8% of cases [Table 1].
Table 1.
Baseline disease and management characteristics of patients (N = 535).
| Variable | n (%) |
|---|---|
| Age in years | |
| Mean ± SD | 34.5 ± 4.7 |
| Median (IQR) | 35 (32–38) |
| Range | 15–40 |
| Age groups | |
| ≤20 | 6 (1.1) |
| 21–30 | 108 (20.2) |
| 31–40 | 421 (78.7) |
| Family history (n = 516) | 122 (23.6) |
| Laterality (n = 516) | |
| Bilateral | 13 (2.5) |
| Unilateral | 50 (9.7) |
| Clinical stage (n = 405) | |
| Stage I (T1) | 39 (9.6) |
| Stage IIA (T0/1 N1, T2 N0) | 99 (24.4) |
| Stage IIB (T2 N1, T3 N0) | 102 (25.2) |
| Stage IIIA (T0/1/2 N2, T3 N1/2) | 77 (19.0) |
| Stage IIIB (T4 or N3) | 56 (13.8) |
| Stage IV | 32 (7.9) |
| Type of surgery (n = 416) | |
| None | 21 (5.0) |
| Modified radical mastectomy | 159 (38.2) |
| WLE + axillary clearance | 94 (22.6) |
| Simple mastectomy | 83 (20.0) |
| Oncoplastic conservative surgery | 22 (5.3) |
| Reconstructive surgery | 34 (8.2) |
| Total mastectomy and axillary clearance | 1 (0.2) |
| Others | 2 (0.5) |
| Reconstruction (n = 535) | |
| Immediate | 7 (1.3) |
| Delayed | 1 (0.2) |
| Histologic grade (n = 428) | |
| I | 18 (4.2) |
| II | 164 (38.3) |
| III | 246 (57.4) |
| Histological type (n = 427) | |
| Invasive ductal carcinoma | 380 (88.84) |
| Invasive lobular carcinoma | 16 (3.80) |
| Mucinous/ colloid carcinoma | 3 (0.71) |
| Medullary carcinoma | 1 (0.24) |
| Papillary carcinoma | 3 (0.71) |
| Paget's disease | 2 (0.48) |
| Ductal and lobular | 1 (0.24) |
| Metaplastic carcinoma | 14 (3.33) |
| Others | 7 (1.66) |
| Tumour biology (n = 348) | |
| ER/PR positive, ERBB2 negative | 154 (44.3) |
| Triple negative | 94 (27.0) |
| Triple positive | 36 (10.3) |
| ER/PR negative, ERBB2 positive | 64 (18.4) |
| Genetic testing (Since 2020) | 58 (10.9) |
| BRCA1 positive | 7 (12.1) |
| Neoadjuvant chemotherapy (n = 417) | 208 (49.9) |
| Radiation (n = 286) | 195 (68.2) |
| Recurrence (n = 525) | |
| Local | 1 (0.2) |
| Distant | 12 (2.4) |
| Survival status (n = 409) | |
| Expired | 11 (2.7) |
| Pregnancy-Associated Breast Cancer | 40 (7.5) |
SD = standard deviation; IQR = interquartile range; WLE = wide local excision; ER = oestrogen receptor; PR = progesterone receptor; ERBB2 = epidermal growth factor receptor 2; BRCA1 = breast cancer gene 1.
Treatment decisions were based on disease extent. Of 417 patients, 208 (49.9%) received neoadjuvant chemotherapy. Modified radical mastectomy was performed in 159 of 416 patients (38.2%), while 94 patients (22.6%) underwent wide local excision with axillary clearance. Oncoplastic breast-conserving surgery was performed in 22 patients, and 8.2% underwent reconstructive procedures. Adjuvant radiotherapy was administered to 68.2% of patients. Recurrence was documented in 13 patients, of whom only one experienced locoregional recurrence, and 11 patients had died by the end of the study period [Table 1].
Kaplan–Meier survival analysis revealed a five-year overall survival rate of 93.9% (95% confidence interval [CI]: 83.0–97.9%). Age-stratified analysis showed that patients aged 31–40 years had the lowest five-year survival rate at 93.1% (95% CI: 79.4–97.8%) [Table 2,Fig. 1].
Table 2.
The 5-year overall survival of patients included in this study according to age (N = 535).
| Risk Factor | 5-year overall survival (95% CI) |
|---|---|
| Age | |
| ≤20 years | 100.0 (REF) |
| 21–30 years | 97.7 (84.6–99.7) |
| 31–40 years | 93.1 (79.4–97.8) |
CI = confidence interval.
Fig. 1.
Kaplan-Meier curve depicting overall survival in young breast cancer patients (N = 535).
Routine referral for genetic counselling was introduced in 2020 in accordance with National Comprehensive Cancer Network (NCCN) guidelines. Among 108 high-risk patients referred, 58 underwent genetic testing, with seven of these found to carry a pathogenic BRCA1 variant [Table 1].
4. Discussion
Breast cancer (BC) is the leading malignancy and primary cause of cancer-related mortality in women under the age of 40, with a reported annual incidence increase of approximately 0.5%.15,16,17 This trend is particularly evident in studies from Asia, where the incidence of young breast cancer (YBC) ranges from 10% to 24% across different populations and healthcare settings.18,19 The definition of YBC varies in the literature, including cut-offs at <35 years, <40 years, or using age as a surrogate for menopausal status.20,21 However, guidelines from the European School of Oncology and the European Society of Medical Oncology define young women with BC as those diagnosed before the age of 40.22
The current study represents a heterogeneous cohort, with 23.9% of all BC cases diagnosed in women aged below 40 years. Notably, 78.7% of these patients were within the 31–40 age bracket. No distinctive ethnic patterns were observed in our cohort compared to similar regional studies within this age group. These findings underscore the importance of recognising age-specific disease characteristics and optimising diagnostic and management strategies tailored to this population.
YBC presents distinct clinical challenges, often characterised by diagnosis at more advanced stages. This delay is frequently attributed to the absence of routine screening in women under 40 and the predominance of self-detected breast lumps, which are typically identified only after reaching a palpable size. Additional diagnostic difficulties, such as dense breast tissue, further impede early detection by obscuring smaller lesions on imaging.23,24 Epidemiological trends have shown that younger women are more likely to present with high-grade tumours and aggressive molecular subtypes, which are associated with less favourable outcomes.17,25,26 For instance, a 2012 study by Azim et al. reported that 34.3% of YBC cases were of the basal-like subtype, while the California Cancer Registry documented a 22.8% prevalence of triple-negative breast cancer (TNBC) in women under 40.27,28 In the current cohort, 27.0% of patients had TNBC and 57.4% had grade III tumours, reaffirming the high-risk profile commonly observed in this age group. Other studies have similarly reported elevated rates of ERBB2-enriched subtypes, lymphovascular invasion, and recurrence among young women.29,30,31
Moreover, YBC is frequently associated with germline mutations, particularly in BRCA genes, which further compound the clinical burden. Previous studies have demonstrated that women diagnosed with BC before the age of 35 have a 9.4% likelihood of carrying a BRCA1 or BRCA2 mutation, compared to a 0.2% baseline risk in the general population.32 Another study identified a significantly higher prevalence of BRCA1 mutations among TNBC patients under the age of 35.33 In the current cohort, 12.1% of those who underwent genetic testing were found to harbour a pathogenic BRCA1 mutation. However, it is important to note that routine genetic testing was only implemented at the researchers' centre in 2020 and remains limited by factors such as low awareness and financial constraints. The cost of testing, alongside the associated burden of surveillance and potential prophylactic interventions, continues to be a significant challenge for both patients and their families.
Treatment of YBC is multifactorial and must account for various prognostic indicators. Clinical trials have reported higher rates of pathological complete response to neoadjuvant chemotherapy among young patients, particularly those with triple-negative breast cancer (TNBC). Nevertheless, this age group continues to experience higher recurrence rates and poorer disease-free survival outcomes. Reported five-year overall survival (5-yr OS) rates in YBC vary significantly across studies, ranging from 61% to 88%.18,34,35 In contrast, the current study demonstrated more favourable outcomes, with a 5-yr OS of 93.9% and only one case of local recurrence. These disparities may reflect underlying differences in tumour biology among ethnically diverse populations, as well as variations in treatment approaches. Literature suggests that advancements in surgical techniques—particularly those aimed at achieving clear surgical margins—and improvements in adjuvant radiotherapy and systemic treatments have contributed to the observed reduction in local recurrence following breast-conserving therapy.36
A previous study conducted at the same institution compared the clinicopathological features of younger and older women, including comparisons with Western populations, and found that 27.4% of participants were aged ≤40 years.37 The younger cohort exhibited a significantly higher likelihood of presenting with metastatic disease, high-grade tumours, and triple-negative biology—findings that are consistent with the current study.
In lower-middle-income countries such as Pakistan, where healthcare expenses are predominantly out-of-pocket, access to comprehensive cancer services remains a substantial challenge. In such settings, patients often prioritise acute treatment over long-term survivorship care, thereby compounding the psychosocial burden of disease. There is a pressing need for national and governmental initiatives to improve access to breast cancer screening for younger women and to develop a deeper understanding of the tumour characteristics specific to this demographic. Such efforts would facilitate the development of contextually relevant treatment guidelines, with a particular emphasis on multidisciplinary management strategies.38
This study highlights the considerable prevalence of YBC in our setting and reinforces the need for targeted research to enhance patient outcomes and quality of life. Several critical areas warrant further exploration. For example, ovarian suppression remains a cornerstone of treatment, but its long-term effects on fertility and overall well-being require more rigorous investigation. Fertility preservation strategies must be optimised to ensure viable reproductive options for young women following treatment. Additionally, genetic testing is essential in guiding personalised treatment plans and preventive strategies for both patients and their families. The psychosocial ramifications of a YBC diagnosis—including emotional distress, body image concerns, and the need for mental health support tailored to younger patients—must also be addressed in future research. Another relevant area is the delay in seeking medical and surgical consultation, which may impact disease progression. Addressing these gaps through focused and systematic investigations will contribute to the refinement of treatment paradigms and improve the standard of care for young women with breast cancer.18,39
This study has several limitations. It was a single-centre study with a retrospective design, which may not be representative of the wider population. Additionally, due to the retrospective nature of the data collection, a substantial proportion of missing data could not be retrieved from the electronic health records. Future research should include larger, multicentre prospective cohort studies to provide more generalisable and comprehensive insights into the epidemiology and management of YBC.
5. Conclusion
The rising incidence of YBC presents a growing challenge for healthcare systems, particularly in resource-limited settings. This study underscores the importance of recognising the unique clinical and pathological features of YBC to inform the development of equitable, age-appropriate cancer care strategies for all affected populations.
Authors' Contribution
Kulsoom Shaikh: Conceptualization, Data Curation, Investigation, Methodology, Writing – review and editing. Aiman Arif: Writing – Original Draft, Writing – review and editing, Formal analysis.
Mehwish Mooghal: Data Curation, Investigation, Methodology. Lubna Vohra: Conceptualization, Supervision, Validation.
Ethics Statement
Ethical approval for this study was obtained from the Ethical Review Committee (ERC) at The Aga Khan University Hospital (AKUH) Karachi, Pakistan with ERC number 2022-7096-22696.
Conflict of Interest
The authors declare no conflicts of interest.
Funding
No funding was received for this study.
Data Availability
Data is available upon reasonable request from the corresponding author.
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Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Data Availability Statement
Data is available upon reasonable request from the corresponding author.