Comments on “Is the incidence of early‐onset cancers increasing in the northeast of Italy? A 30‐year analysis of the regional cancer registration data by age, 1987–2019”

We would like to comment on the article entitled “Is the incidence of early-onset cancers increasing in the northeast of Italy? A 30-year analysis of the regional cancer registration data by age, 1987–2019” by Buja et al., recently published in the Journal.1 In Italy, the incidence trend of early-onset breast cancer is frequently debated but poorly defined. We are former (L.B.) and current members of the coordinating board of the Italian Group for Mammography Screening (Gruppo Italiano per lo Screening Mammografico, GISMa), the scientific society that brings together the health professionals involved in local mammography screening programmes. We often receive communications from our associates expressing their concern for a supposedly strong increase in breast cancer incidence they see among younger women. In fact, there is no sound evidence that this uptrend is currently ongoing. Buja et al. studied women aged up to 49 years living in a large administrative region of north-eastern Italy and found a consistent increase in incidence between 1987 and 2003 followed by a stabilisation. In the last 10 years, in the absence of a nationwide research effort, five more studies have been reported using data from single local cancer registries or pools of registries with varying composition and population coverage.2-6 Their heterogeneity as to time period and length of observation does not allow for a comprehensive evaluation of their results. The largest annual incidence increase reported among women aged <50 years was 1.6% (2008–2016).3 In two studies, the increase was more modest, 0.3% (2003–2014)2 and 0.8% (2013–2017).6 In another one (2008–2017), the upward trend ceased in the middle 2010s.5 In a small area of northern Italy, the rate was reported to be stable in the mid-term (1996–2021).4 The first question we have to ask ourselves is whether an increasing incidence trend of breast cancer in younger Italian women—if any—would be plausible. The answer may be: yes, but not completely. There could be two potential underlying causes behind an increasing trend, namely: the biasing effect of early detection through organised and spontaneous/opportunistic screening and a true increase in exposure to risk factors. The age-period-cohort modelling analysis is theoretically capable of disentangling variations in the occurrence of breast cancer resulting from these two processes. In fact, the overall prevalence of screening activities is virtually impossible to measure. Screening of women aged 45–49 years has been implemented in a few administrative regions and at different points in time, although current Italian guidelines already suggest this practice. For spontaneous/opportunistic screening, by definition, no original data exist. Additionally, in dense breast tissue, the likelihood of generating lead time (the time by which screening advances detection) decreases, and we know that generating lead time is the sine qua non of an impact on breast cancer incidence. The diffusion of the idea of risk-based screening, however, is expected to lead to over-investigation of younger women at high risk of disease, with an improvement of sensitivity for early breast cancer. As far as risk factors are concerned, younger generations worldwide have been exposed over the last four decades to an increasing prevalence of obesity. Between 1995 and 2014, the risk of young adult Americans (age 25–49 years) developing six types of obesity-related cancer has increased, but breast cancer was not among them.7 It is known that risk factors for pre-and post-menopausal breast cancer are not perfectly overlapping. In particular, obesity is a risk factor only for post-menopausal breast cancer and, with respect to pre-menopausal disease, nulliparity is protective.8 Despite this, a study from northern Italy has shown a rapidly increasing incidence trend of ductal carcinoma in situ among women aged 45–49 years.9 This resulted from an increased detection of ductal carcinoma in situ through the local organised screening programme but also from an uptrend in the risk of diagnosis, which can be explained with a mid-term change in diagnostic scrutiny independent of the programme, or an increased exposure to risk factors, or both. However, it remains the fact that risk factors for ductal carcinoma in situ and invasive carcinoma of the breast are partly different.10 This means that their trends might not be directly related to each other. In any case, assuming that a marginal incidence increase is underway, the growth rate would be so low as to make the trend not perceptible unless it is represented statistically. So the second question to which we have to provide an answer is why clinical doctors have the perception of a rapid increase. We raise two closely interrelated hypotheses. First, the process of creation of specialist Breast Centres, coupled with the budget constraints and the staff shortages facing healthcare institutions in Italy, has the two-fold effect of pushing towards the centralisation of breast care services and increasing the patient workload per physician in the referral centres. The growing access of younger patients, who have peculiar clinical and psychosocial needs and more life years to lose, is more noticeable. Under these conditions, the appreciation of the temporal trend of breast cancer may well be deformed. And second, the Italian medical education system and the healthcare system have so far failed to promote a better understanding of the epidemiology of chronic disease by clinical doctors, including the interpretation of the measures of disease occurrence and of related biases and confounding. Consequently, the great deal of incidence data made available by cancer registration remains unused, if not ignored, and clinical doctors are dependent for updating their knowledge on the information provided by other actors. Bridging this gap is essential to avoid misconceptions about breast cancer trends in younger women. Lauro Bucchi: Conceptualization; investigation; writing – original draft; writing – review and editing. Stefano Ferretti: Conceptualization; investigation; writing – original draft; writing – review and editing. Valentina Bordon: Conceptualization; investigation; writing – original draft; writing – review and editing. Francesca Caumo: Conceptualization; investigation; writing – original draft; writing – review and editing. Veronica Girardi: Conceptualization; investigation; writing – original draft; writing – review and editing. Simona Grossi: Conceptualization; investigation; writing – original draft; writing – review and editing. Diego Iemmi: Conceptualization; investigation; writing – original draft; writing – review and editing. Marzia Muzi: Conceptualization; investigation; writing – original draft; writing – review and editing. Valentina Ravaglia: Conceptualization; investigation; writing – original draft; writing – review and editing. Gianni Saguatti: Conceptualization; investigation; writing – original draft; writing – review and editing. Alfredo Santinelli: Conceptualization; investigation; writing – original draft; writing – review and editing. Valentina Sini: Conceptualization; investigation; writing – original draft; writing – review and editing. Silvia Deandrea: Conceptualization; investigation; writing – original draft; writing – review and editing. The authors declare no conflicts of interest.