Risk factors for breast cancer and their association with molecular subtypes in a population of Northeast Brazil

1

Introduction

According to the World Health Organization (WHO) in 2018 an estimated number of 2,088,849 new BC cases contributed to 11.6% of all cancer deaths worldwide [1] . An increase of BC was mostly observed in developing countries due to changing lifestyles and longer life expectancies, whereas in most developed countries, the incidence remained stable or even declined [2] . With more than 209 million inhabitants, Brazil is the largest country in Latin America and BC is currently contributing to 29.5% of all neoplasms among women [3] . For the time from 2020 to 2022 the National Institute of Cancer predicted 66,280 new cases for each of the years [3] . In the two largest urban centres of Brazil, namely, São Paulo and Rio de Janeiro, and in other regions in southern, southeastern and midwestern Brazil, the incidence of BC has stabilised over the last 10 years [3] . This is in contrast to the northeastern region, where the incidence of BC increased between 2005 and 2021 from 27.23 to 44.29 new cases per 100,000 women [34] .

In the literature, it is well established that reproductive, anthropometric and lifestyle-related factors modify the risk of BC 5678 . It was estimated that approximately one-third of all post-menopausal BC cases in the United States are caused by modifiable and therefore preventable lifestyle-related risk factors [9] . In the United Kingdom, 6.9% of all BC cases were attributed to obesity and overweight as a single risk factor for the disease [6] . Obesity was associated with increased risk of BC among post-menopause women, whereas an inverted association was identified for pre-menopause women [5] . Additionally, risk factors can be differentially associated with molecular BC subtypes. Obesity and overweight of premenopausal women, respectively, several reproductive risk factors, were associated with the triple negative molecular BC (TNBC) subtype, that is defined by the absence of expression of hormone receptors and HER2/NEU 101112 . Compared to other molecular subtypes the therapeutic opportunities for treatment of TNBC are reduced and the high graded, aggressive tumours have a poor prognosis [13] .

Previous Brazilian case-control BC studies addressed on anthropometric measures, life-style related risk factors and family history 141516171819202122232425 . With the exception of a database study by Menezes et al. [16] all of these studies referred to data from populations in the southern, south-eastern and central eastern regions of Brazil. Only few studies addressing the identification of risk factors, were performed in north-eastern Brazil, a region where BC incidence is increasing [2627] . Furthermore, possible associations between TNBC, respectively other molecular subtypes and risk factors, so far were only addressed in one single Brazilian case-case study [28] . The frequency of TNBC in the Brazilian Northeast region varied from 16.1% to 17.4% and was more common among premenopausal patients, respectively patients aged ≤ 40 years if compared to other molecular subtypes 282930 .

Since 2003, Brazil has had a public programme for the early detection of breast cancer, and mammography screening has been promoted in the month of October (“Outubro rosa”). In northeastern Brazil, most women rely on information about BC from television, and very little information is provided about preventable risk factors that can be modified to decrease the risk of BC. There is an urgent need to identify risk factors for BC and TNBC in this population and, if these factors are modifiable, to promote their prevention in health campaigns. The present study focused on the identification of BC risk factors in a population from northeastern Brazil and the association of risk factors with TNBC and other molecular subtypes.