Understanding the Rising Breast Cancer Among Young Women: Biological Insights, Projections, and an Opportunity Window Leading up to 2040

Abstract

Breast cancer is the most common cancer affecting women globally, with an increasing incidence of breast cancer in young women in India and worldwide. Despite medical advancements, the lifetime risk of developing breast cancer is still high. The emergence of breast cancer in young women is now acknowledged as a distinct entity characterized by unique clinical and biological features and an overall poor prognosis. This article discusses the changing landscape of breast cancer in young women in India and globally, potential examples of the underlying reasons, and possible strategies to start reversing the current upward trend.

With 2.26 million new cases recorded in 2020, breast cancer emerges as the most prevalent cancer affecting women across the globe, including 178,000 in India [1]. A concerning trend is the increasing incidence of breast cancer in young women, defined as 40 years old or younger, in India and globally [1–9]. Despite remarkable medical and technological advancements that have positively impacted breast cancer mortality and survival in many countries, the lifetime cumulative risk of developing breast cancer by age 75 is still high—3% in India and 5% globally, according to recent data from Cancer Atlas [5]. Further, the benefits of these advances have not adequately reached young women confronting this diagnosis. The emergence of breast cancer in young women is now acknowledged as a distinct entity characterized by unique clinical and biological features and an overall poor prognosis. Some insights into the changing landscape of breast cancer in young women in India projecting into 2040 are being presented here. The article aims to uncover the underlying reasons and biological factors driving the surge in breast cancer cases among this demographic. In addition, I also aspires to discuss potential strategies to reverse the current upward trend to save the lives of the youth and young women from breast cancer tomorrow.

Breast Cancer in Young Women (BCYW)

Breast cancer in young women (BCYW) cases are increasing in India and globally for poorly understood reasons, including its tumor biology. The biological basis and triggers that initiate the pre-oncogenic process leading to BCYW are still being studied. According to the World Health Organization’s (WHO) 2020 data, breast cancer accounts for approximately 26.29% of all cancer cases in Indian women, which is somewhat like the global average of 24.5% when age is considered under 39 [1]. However, the percentage of new cases among women under 39 in India is higher than the global incidence. It stands at approximately 15.69% up to age 85, compared to the worldwide incidence of 10.96% in this age group (Fig. 1A), pointing to geo-disparities. Likewise, the percentage of BCYW cases out of total breast cancer cases varies across different cancer centers in India, for example, 16.7% in a study from TATA Memorial Center Mumbai and 35.6% from King George Medical University Lucknow’s study [8, 10].

Fig. 1.

Breast cancer in young women trend: A Prevalence of breast cancer under 39, 40–44, and 45–85 + age groups in India and worldwide in 2020. B Distribution of breast cancer in young women under 39 across age groups in India. C Status of breast cancer < 39, < 44, and < 85 years in India and worldwide in 2020 and projected breast cancer numbers through 2040. Upper insert, ASR per 100,000 for breast cancer < 39, < 44, and < 85 years in India and USA in 1984 and 2012. K, thousand; M, millions; ASR, age-standardized incident rates (world) per 100,000. *Subnational data. Lower insert, Percentage of females aged 20–39 and 20–44, and total female population under 100 years for 1984, 2012, 2020, and projected 2040-P (projected) as per population pyramid data, reference 14. All illustrated breast cancer data is derived from the WHO’s Global Cancer Observatory, ref. 1.

Because about 65% of the population in India is under 35 [6], breast cancer under the age of 39 is a growing concern [7]. Studies show that most cases fall within the age range of 34–39, while occurrences in younger age groups such as 20–24, 25–29, or 30–34 are not uncommon, with an average age of 33.65 years (Fig. 1B). India’s age-standardized rate per 100,000 (ASR) for breast cancer in BCYW under 39 is 5, which is lower than the global average of 8.2. Nevertheless, the rate is still higher than in many other countries, which was 3.5 in 1984 and 3.7 in 2012 for India, following an upward trend reaching 5 in 2020 (Fig. 1C, upper insert). Breast cancer was not a widely recognized form of cancer in 1984. In comparison, the United States had an ASR of 9.5 in 1984 and 9.1 in 2012 (Fig. 1C, upper insert). This might suggest that the current trend of breast cancer in young women might be a recent occurrence.

According to the WHO, the number of breast cancer cases in young women is expected to increase globally, of which 11.87% will be from India by 2040 (Fig. 1C). A comparison of the relative percentage of females aged 20–39 from 1984 to projected 2040 (Fig. 1C, lower inset) suggests that the rise in population is not the main reason behind the BCYW trend in India. There is a biological basis for this trend. The fact that BCYW status in India is lower than in the rest of the world does not put the concerned professionals in a comfortable zone, given the BCYW trend over the past four decades.

What Sets BCYW Apart

Breast cancer in young women poses unique medical and non-medical challenges distinct from older age groups [2–4, 7–12]. Extensive research reveals BCYW as a distinct biological subset of premenopausal breast cancer, often with aggressive subtypes like triple-negative breast cancer TNBC/basal, HER2-positive, and luminal B. The rise in BCYW challenges the notion that breast cancer is solely an aging-related disease, emphasizing that age is not the sole predictor for this demography. Unfortunately, BCYW patients face a poorer prognosis due to aggressive subtypes and late-stage diagnoses. Underlying cellular reasons for this remain unclear, possibly involving aggressive biological and genomic characteristics [3, 4]. In addition, the clinical outcome for some, if not all, BCYW cases might also be affected by the lack of data from clinical trials involving younger women [9]. The current guidelines for managing BCYW are generally based on historical breast cancer randomized trials that did not include many women in the younger age group. Additionally, albeit BCYW awareness in this demography, unclear screening guidelines, and the exclusion of younger women from public screening programs might also contribute to delayed detection. A lack of understanding about self-breast care and the misconception that breast cancer mainly affects older women further compound these challenges [7–12].

Breast cancer in the early stages of a woman’s life brings unique challenges, including disruptions to career paths, financial strain, a young family or about to start the family, the impact of specific treatment regimens on their body (i.e., fertility, early menopause, and losing their breasts or hair), and the fear of recurrence due to long breast tumor dormancy. In addition, some young women may experience dismissal from healthcare providers who tend to overlook suspicious signs or adopt a wait-and-see approach based on the patient’s young age [13]. Diagnostic delays—irrespective of underlying patient—and provider-centered reasons are particularly consequential, as breast tumors in younger patients exhibit faster growth rates, leading to more aggressive stages and prolonged suffering. In brief, young women are entrusted with maintaining their breast health and promptly detecting any irregularities—a critical step in early detection that could save lives.

Why Are More Young Women Getting Breast Cancer

A close review of the BCYW trend since 1984 reveals an increasing incidence of BCYW cases in India (as well as globally). However, many questions remain unanswered: why are more young women getting breast cancer? What is causing this increase? In this context, sometimes erroneously, it is assumed that this is due to the population growth of young women under 40 in India, increased breast cancer awareness, and better diagnostic procedures. However, a closer analysis of the comparative population pyramid [14] and data for the 20–39 age group females in India suggests that this might not be the case (Fig. 1D). Similarly, a large body of literature about breast cancer awareness in the youth and young women in India indicates an overall disappointing albeit awareness for BCYW and self-breast care in this age group who might still tend to believe that breast cancer might be a disease of older women. Likewise, this demography is generally excluded from public screening programs.

Further, given that only about 10% of BCYW cases are estimated to have a predisposition to breast cancer-promoting genes [3], the noted increase in BCYW cannot fully account for these variables. In addition, these factors do not fully explain the cellular basis and causative triggers of BCYW to turn on the process of pre-oncogenesis. The underlying reasons are multifactorial and are exerted over several years before the disease. The cells in the breasts are influenced by internal signals within the body and external modifying factors like lifestyle choices, carcinogens, and environmental factors (Fig. 2A, B). In addition, dysregulation of cellular homeostasis in the breast balances the influence of protective vs. risk factors on the biology of breast cancer–driving pathways (Fig. 2A, for example).

Fig. 2.

Changing trend of breast cancer in young women: A A simplistic representation of the troubling trend of increasing cases of BCYW, protective and risk factors, and broad mechanisms. B Window of susceptibility from puberty to adolescence and representative relevant observations. C BCYW under 39 trends from 2020 through 2040.

Risk Factors and BCYW

Breast cancer, a hormonally regulated condition, typically appears after menopause. The process of developing breast cancer is complex and takes several years. It involves transforming normal breast cells into cancerous ones—due to the dysregulation of genetic, cellular, and epigenetic pathways. During breast development, estrogen plays a crucial role in maintaining the balance of cells and tissues. The ovary, adipose tissue, and placenta mainly produce it. Estrogen levels in the body typically undergo consistent fluctuations from puberty through menopause. Disruption or excessive stimulation of estrogenic signals can result in uncontrolled cell growth. Additionally, estrogenic signaling is now known to contribute to the amplification of oncogenes, thus further fueling the process of breast cancer oncogenesis [15, 16].

The mammary gland undergoes unique developmental features and cyclic remodeling, delicately controlled by hormonal interplays. Various reproductive and extrinsic risk factors, including xenoestrogens, can also influence this process. Apart from the risk factors depicted in Fig. 2, many other risk factors have been associated with breast cancer. It has been found in a recent study that there are more than 900 chemicals that can cause breast cancer [17]. In general, most studies on the risk factors of breast cancer are epidemiological and not supported by experimental data that can prove cause-and-effect relationships. Additionally, these studies do not always consider the interactions among different risk factors in the context of breast cancer disease outcomes [3]. Since this topic is quite vast, I will be discussing about two examples of risk factors associated with breast cancer in young women.

Late Pregnancies and Breast Cancer Risk

Over the past 50 years, epidemiological and experimental studies consistently emphasize two critical factors influencing a woman’s breast cancer risk: the age at which she has her first child and the timing of pregnancy. Early childbirth and multiple pregnancies reduce the risk, particularly for HR + breast cancer. However, this protection diminishes with delayed childbirth, contributing to breast cancer risk later in life. Recently, women have been delaying childbirth for various reasons, the discussion of which is beyond the scope here. This delay might be associated with an elevated risk of future breast cancer. Recent data suggest that such risk might be linked to an accumulation of cancer-linked mutations in mammary gland cells isolated from healthy women ranging from < 25 to 55 years, with genomic sequencing estimating 15 mutations in the epithelium and 42 in the stroma for women aged 35–55, compared to those with early pregnancies in < 25 or 25–34 years. The pregnancy hormones may further expand specific clonal populations with cancer-relevant mutations, promoting oncogenesis [18].

Paraben and Phthalate-containing Personal Care Products

Exposure to a specific type of environmental chemicals, called xenoestrogens, has been shown to increase the risk of developing breast cancer. This is because these chemicals act like estrogen in the body and stimulate cellular pathways, which can lead to cancer. For instance, parabens and phthalates are commonly used as preservatives and plasticizers in personal care products (PCP), and they have been linked to breast cancer in some cases. Xenoestrogens in personal care products (PCP), like parabens and phthalates, heighten breast cancer risk through estrogenic activities. In a recent study [19], reducing PCP use with these substances for 28 days in healthy women showed a reduction in the levels of breast cancer–related genes and activities. Thus, parabens or phthalates in PCPs could contribute to estrogenic overstimulation of breast cancer pathways. Given widespread PCP use by young women, it might be a risk factor for BCYW.

Paramount Importance of Events from Puberty to Adolescence for BCYW

During puberty and subsequent stages of breast development until adolescence, the process of breast development undergoes periodic remodeling—controlled by hormonal signals, biological interplays, and other factors that play a crucial role in maintaining optimal breast health [3]. During this phase, the susceptibility of breast cells to internal and external factors increases significantly. The cells in the breasts are influenced by various internal signals within the body (i.e., inflammation and oxidative damage) and external factors such as lifestyle choices, environmental factors, and carcinogens, which can modify the inner workings of different cell types in the breasts and contribute to the development of cancer. In short, several internal and external factors can modify breast development and increase the risk of breast cancer in young women. Emerging data suggest that modifiable lifestyle factors from puberty to adolescence shape the biological determinants of breast cancer characteristics.

It has been observed that events occurring during puberty and adolescence can influence the development of breast cancer later in life. This is, in part, because breast cancer typically takes years to develop before it becomes apparent. Furthermore, studies have shown that cancer-associated pathways can be dysregulated in normal breast tissues, even in young women, which may contribute to the development of breast cancer later in life. The increasing prevalence of breast cancer among young women in their 20 s or 30 s raises the possibility that events leading into or during adolescence play a role in breast cancer development in BCYW. Scientists are trying to understand if certain breast cancer–genetic changes in specific cell types in the normal breast could potentially lead to breast cancer later in life. Here, I exemplified three such 2023 discoveries that emphasize the significance of puberty in understanding both the genesis and rise of breast cancer in young women.

Luminal A-linked Genetic Alterations in Normal Breast Tissues

Genetic studies reveal the del (1;16) chromosome alteration in the luminal A breast cancer subtype, present in normal breast tissues during puberty to adolescence [20]. These changes take about 10.6 years to accumulate before cancer manifests, with initial signs appearing in one’s 20 s or early 30 s. A significant number of young women who are diagnosed with breast cancer are found to have the luminal A subtype. It remains possible that by studying similar early molecular changes and understanding the factors that trigger them. This will help our understanding of BCYW and develop preventive strategies for at-risk young women. This could pave the way for personalized interventions to mitigate their risk.

Processed Foods and Mammary Gland Abnormalities

Cancer researchers have recognized for a long time that processed foods have a significant impact on breast cancer due to the high content of advanced glycation end products (AGEs) they contain. These AGE compounds can form inside our bodies or be present in processed foods or products cooked at high temperatures. AGEs activate prolonged inflammation signaling, oxidation, and promoting epithelium-stroma interactions—all linked to cancer development. Recent research has shown that mice fed a diet high in AGEs during puberty experienced unusual growth patterns in their mammary glands [21]. These growth patterns were like the early stages of breast cancer, and they persisted into adulthood. Regular or low AGE diets did not have the same effect. The study highlights the critical role of puberty in adolescence when mammary glands are highly susceptible to external influences. This can potentially increase the risk of breast cancer later in life.

Resurfaced Connections Between Birth Control Pills

Debates on breast cancer risks in young women often focus on birth control pills, weighing benefits against potential drawbacks. Synthetic hormones in these pills can disrupt the hormonal balance, affecting the secretion of hormones in circulations and increasing the risk of breast cancer. According to a study [22], different types of hormonal contraceptives can raise the risk of breast cancer by 20–30% in comparison to non-users. The study also revealed that women who use oral contraceptives for 5 years have an additional risk of developing breast cancer over 15 years. The risk varies from eight cases per 100,000 women (ages 16–20) to 265 cases per 100,000 women (ages 35–39).

Why BCYW Is Vital for Women’s Health at this Point in India

The core of breast healthcare lies in the vital connection between women’s health and breast cancer. India’s demographic landscape suggests a median age of about 28.7 years, 42% under 25 years, 65% under 35 years, and 32.0% of females under 39 years [6, 14]. Under 39 cases comprise about 15.69% in India and 10.96% worldwide. BCYW < 39 years cases in India are not projected to decline until the year 2040 with a mean age of 33.88, suggesting that those who might be diagnosed with breast cancer in the year 2040 might be around 17.88 years old at the present date, i.e., 2024 (Fig. 2C). This offers an opportunity for targeted grassroots awareness programs, focusing on our youth women transitioning from puberty to adolescence and creating a national awareness about modifiable preventable measures during this period.

Previous studies in India suggest albeit-to-disappointing awareness about BCYW and self-breast care—the single most driving reason for all other aspects of breast health, including prompting young women to seek advice from healthcare providers. In this context, the National NCD screening program targets a subset of young women > 35. Recent studies suggest that the mortality rate of young women under 40 has stopped declining, as opposed to the 40–79 years age group in the United States [23], in part due to distant metastasis [3]. However, we lack similar data from India for different demographics. In addition, no randomized trials have been published to directly evaluate the impact of the awareness level on mortality for women under 40 in India or globally.

Because of growing incidences of BCYW in India (and globally), young women understanding their bodies and detecting irregularities early is crucial for saving lives tomorrow. In this context, one of the ongoing programs of the BCYW Foundation is to sensitize the youth population at a grassroots level about breast health and self-breast care through targeted programs and structured local chapters led by youth volunteers and local mentors to ensure effective implementation of the program [7]. Encouraging young women to understand their bodies and detect irregularities early is crucial for saving lives tomorrow. Ideally, every young woman should be aware of her breast cancer risk if possible. Equally important might be to promote targeted BCYW awareness throughout the year, not only during Breast Cancer Awareness Month in October [11].

Conclusions

The preceding discussion underscores the critical importance of heightened targeted awareness, proactive self-breast care, and inclusiveness of young women with clinical trials in counteracting an upward trend of BCYW. The necessity of early detection cannot be overstated, particularly in saving the lives of young women. However, this goal is intrinsically linked to increasing awareness early and fostering a culture of lifelong prevention.

Furthermore, empowering young women to understand their bodies and recognize any irregularities early is equally vital. Knowledge about one’s breast cancer risk, coupled with a better understanding of the influence of developmental stages from puberty to adolescence on breast cancer later in life, is essential. Such awareness can significantly contribute to early detection and potentially lead to life-saving interventions.

Lastly, the inclusiveness of BCYW in emerging breast cancer clinical trials should also help the prognosis. Historically, younger women have been underrepresented in randomized trials concerning breast cancer, leading to a gap in our understanding of its biology and treatment responsiveness in this demographic. To bridge this gap, including young women in clinical trials, is essential, enhancing our knowledge and improving this population’s outcome and treatment options.

To conclude, if we focus on these crucial aspects—creating awareness at the grassroots level, promoting self-breast care, encouraging lifestyle changes that can prevent breast cancer from puberty to adolescence, and ensuring the inclusion of young women in clinical studies—we can significantly reduce the impact of breast cancer on young women’s health and well-being.

Declarations

Conflict of Interest

The author declares no competing interests.