Breast cancer incidence rates have been increasing in many countries in Asia, Africa, and South America. According to the recent Population Cancer Registry Golestan (GPCR) report, a rapid increase in age-specific incidence rates of breast cancer has been reported. About 7% of all breast cancers diagnosed in the United States are in young woman with less than 40 years. Although the incidence of breast cancer in younger women is lower than in elderly women, it is known that their related risk factors are distinct [7, 17].
The Age standardized rate (ASR) in our study ranged from 3.0 to 5.3, which is less than the data released by GLOBALCAN, where the ASR in the World was 8.3% and in Brazil 10.8%. Therefore, the incidence in Rio Grande do Norte was stable, unlike the situation in other cities in Brazil, such as Porto Alegre and Goiânia, which had a variation in the incidence rate from one year to the next of 4.6 and 4.4%, respectively [18].
For the last decade, breast cancer incidence and mortality among young women from Middle Income Countries (such as Brazil and Bolivia) is increasing. In one Brazilian study, the Average Annual Percentage Change (AAPC) was 5.22%, 5.53% and 4.54% for the age groups up to 39, 40 to 59 and 60 years and over, respectively [19]. Of the five Brazilian regions, the Northeast, which is less economically favored, stands out with the highest increase in breast cancer mortality among women aged 20 to 49 years old in the period 1996 to 2013. This is related to late diagnosis and less modern treatments available in the public sector, since women in the public sector present with a higher initial stage at the time of diagnosis, when compared to the private sector. [3, 14]
In Colombia, Cardona e Agudelo [20] observed an upward trend in breast cancer mortality rates in women 20–44 years from 1994 to 2003, although the mortality rates from this cancer in women 45–64 years remained constant during the same period. An increase in breast cancer mortality rates was also observed in Iran from 1995 to 2004 and was greater in women 15–49 years compared to 50 years. The same trend can be observed in China, with an Average Annual Percentage Change (AAPC) of 2.9 (95%CI: 2.5–3.4) in breast cancer incidence in women 15–49 years from 1973 to 2005 [21]. In a developed country, such as the United States, an increase in breast cancer incidence in women with 25–35 years with metastasis was observed from 1976 to 2009 (AAPC 2.07; 95%CI: 1.57–2.58), the same in France (1991–2003) in women up to 49 years [22] and in Spain (1980–2004) in women 25–44 years [23].
South America has a cancer incidence rate of 56.8 per 100,000 women, high when compared to Australia / New Zealand, Europe and North America [4, 24]. This is probably due to differences in the prevalence of risk factors, such as family history, reproductive factors and lifestyle, in addition to access to early detection, including screening [3, 7]. In our study, the result of women < 40 years of age with breast cancer is approximately 13% in relation to the total number of cases and, despite stabilizing over the years analyzed, differing from the data of the countries mentioned, it shows that the number of young women in our service is compatible with the global one (Table 1).
Consistent with other studies, we observed the incidence rates significantly higher among women living in urban areas than among women in rural areas [25, 26]. The reasons for these differences are: diagnostic bias, as women in urban areas have easier access to health services [27, 28], as well as the distinction related to lifestyle, reproduction, overweight, and obesity [29–31].
As for the level of education, 66.6% of the patients had only high school. This data points to an impairment due to a low level of education and limited access to information about how to avoid the disease, perform self-examination, and the importance of early diagnosis [7]. Additionally, there may be an association with rural residence, less access to hormonal contraceptives, greater parity and longer breastfeeding periods, which provide greater protection against breast cancer [4].
Although there is a predominance of patients aged 30–40 years, we observed a shorter survival in younger patients (< 30 years). Studies have shown that women with breast cancer diagnosed at younger ages more often have a genetic predisposition to the disease and tend to have more aggressive tumors [32–35].
Our patients were mainly diagnosed with invasive carcinoma of no special type (87%), stage II (34.2%), positive for the progesterone receptor (PR, 51.6%), and for estrogen receptor (ER, 59.1%), positive family history of cancer (44.5%). The worst 10y-OS was observed in patients with < 30 years, negatives for ER and PR, tumor stage IV and nulliparous. Younger women have more aggressive disease, including higher stages, negative hormone receptors, increased basal-like subtypes, lymph node positivity, and larger tumors. The factors of pre- and postmenopausal women differ because, in that same study, it was shown that the higher waist to hip ratio was associated with a reduced risk of breast cancer among young women, but with a high risk among older women [18, 24, 36].
There is a better therapeutic response for woman with ER/PR + tumors due to hormone therapy [6], and conversely, triple negative molecular subtype has a worse prognosis, since it is significantly more aggressive, recurrent and without effective therapy [5, 24, 36, 37].
Analyzing the parity status, a lower survival is observed in those who never had children. This factor is predictable, because according to the American Cancer Society (2019) [32], parity before the age of 30 and breastfeeding are protective factors for women [37, 38]. Parity was associated with an increased risk among young women and a reduced risk among older women, while breastfeeding was protective for young women. In comparison, when stratified by age, menopausal status was not associated with distinct risk factors or characteristic tumor profiles [35].
A total of 91% of patients underwent mastectomy, much more than conservative surgery, which can be related to the fact 49,7% of the patients were diagnosed at stage III/IV (N = 302). Mastectomy at early stages no longer corresponds to longer survival, because quadrantectomy associated with other therapies can provide the same effect with a significant reduction in the psychosocial impact on the woman's quality of life [38, 39].
Based on these results, it is necessary to rethink the screening policies to be more accessible and include young women, such as to offer annual clinical breast examination and imaging exams.
Finally, the incidence of young woman diagnosed with breast cancer in our cohort was low and did not increase for the last 10 years. This observation could be explained due to the subdivision of hospitals that provide cancer care in the state of Rio Grande do Norte. The State is divided into eight Health Regions, or four macro-regions. The hospital where this study was conducted is a philanthropic institution responsible for oncologic care in the metropolitan macro-region corresponding to regions I, III, V and VII, or 64.1% of the state's population. There are three hospitals that attend in more rural regions, collaborating for a greater coverage of the oncologic population.