Breast cancer (BC) is the leading cause of cancer-associated amongst women worldwide. Considering the most updated data on BC from 2020, 2.261.419 new cases of BC were registered worldwide (accounting for 24.5% of all tumours in women). Of these, 531,086 cases (25.8%) in Europe were detected, with 55,133 new diagnoses (28.1%) in Italy (1).

BC is a multifactorial disease; however, the different risk factors established for pathological development do not fully explain the aetiology of the disease. The results of several studies showed that individual, environmental and occupational factors serve a critical role in the onset of this pathology (2-6). In women, the most common individual risk factors causing hereditary BC are genetic mutations involving the BRCA1 or BRCA2 genes. However, there are also less common inherited mutations in other genes, including ATM, TP53, CHEK2, PTEN, CDH1, STK11 and PALB2(7). Lifestyle is an important risk factor, with lack of physical activity, excessive consumption of alcohol, a high body mass index (BMI), a high-fat diet and smoking all increasing the risk (2,8-11). Ethnicity, age and socio-economic status can influence the risk of developing BC. White women exhibit the highest incidence of BC, followed by Black, Asian and Hispanic women. This could be explained by racial and socioeconomic barriers to early detection and screening, and unequal access to treatment, as well as differences in lifestyles (12-16). Other individual factors are attributable to procreative aspects, such as the onset of menarche and menopause, as well as the age of first pregnancy with breastfeeding (17-19). Last but not least, a familiar BC and/or general predisposition to cancer may represent important risk factors (17,18), such as chronic fatigue, sleep disturbance and depression (20-22). Several studies have investigated the gene-environment interactions showing that BC risk is related to the common susceptibility variants, which can be altered by environmental factors, such as industrial air pollutants, soil or water contamination due to heavy metals and genotoxic agents, active or passive tobacco smoke (3,10,23-34). Finally, several occupational factors can expose workers to a higher risk of BC due to toxic compounds or exposure to ionising radiation, rotating night shifts or higher-status occupations (35-42).

This last association between BC and occupational factors is a topical issue, since it is estimated that exposure to occupational hazards causes up to 8% of cancers (37,43,44).

According to data from the seventh European Working Conditions Survey in 2020, 13 and 15% of female workers, in Italy (ITA) and European Union (EU) respectively, declared exposure to chemical products or substances for at least 25% of the time in the workplace. Moreover, 10% (ITA) and 14% (EU) of women stated they worked ≥1 time a month at night, whereas 18% (ITA) and 21% (EU) declared to perform work shifts (45).

Occupational exposure to rotating or night shifts could lead to the onset of tumours such as BC (46,47). In fact, in 2019, the International Agency for Research on Cancer (IARC) published a monograph that considered the relationship between night shift work and carcinogenesis. Based on both epidemiological and experimental scientific contributions on animals, the IARC Working Group defined night shift work, which causes an alteration of circadian rhythms, as a probable human carcinogen, with classification 2A (limited scientific evidence in humans, but sufficient evidence in animals) (48).

Although the results of the latest studies are controversial, the main pathogenetic hypothesis is based on the impact that night shift work and night light exposure could have on the rhythmicity of the circadian biological functions (49,50). These alterations result in disturbance of circadian rhythms, reduction of melatonin production and sleep perturbation, affecting several metabolic and physiological processes, including hormone synthesis and cell cycle progression (51-54).

Amongst the several mechanisms proposed to determine the effects of artificial light at night on BC, the majority seem to highlight the importance of inhibition of melatonin secretion during the night due to sleep deprivation, resulting in chronodisruption (55). In women performing shift or night work, melatonin secretion is inhibited by light, resulting in an increase in estrogen, since it has a significant anti-estrogenic activity (54,56).

This multifaceted hypothesis may explain why night workers may have a greater risk of developing BC compared to the general population (42,52,55,57) and why work organisations should implement a strategic procedure to prevent BC. Under these premises and also in light of the new evidence, this review aims to provide an overview of the most relevant risk factors, providing recommendations to fill gaps in risk assessment and suggest novel organisational strategies that occupational physicians should adopt in the workplace, both for the prevention and return-to-work process of female workers affected by BC.

The review was performed by searching PubMed, Scopus and Web of Science databases. The inclusion criteria were: Full-text studies, published in English, published between 2015-2021, and studies associating BC risk with occupational factors, particularly shift and night work. Certain studies, although methodologically sound, were excluded as they were considered irrelevant to the purpose of the study. Most articles were found using the terms: ‘breast cancer’ AND ‘night shift’ OR ‘breast cancer’ AND ‘night shift work’ OR ‘breast cancer’ AND ‘occupational exposure’ OR ‘breast cancer’ AND ‘occupational risk’. No restrictions were applied to the country of origin or ethnicity of the patients recruited. Furthermore, based on titles and abstracts, the relevance of the topic and admissibility of all the retrieved publications were further assessed. Finally, further relevant studies were identified through manual screening of the selected articles' reference lists and recently published reviews.

In work schedules characterized by night shifts, the occupational physicians can play a key role both in risk assessment and in prevention strategies. In particular, when workers susceptible to BC are employed, healthcare professionals can provide strategic contributions for primary prevention, health promotion and return to work. Primary prevention has different targets, such as adequately assessing the suitability for shift work, organising shifts according to ergonomic criteria, and adopting adequate compensatory measures to avoid significant disturbances in circadian rhythms, accumulation of sleep loss and conflicts in social life. Although certain pathologies can constitute a handicap for rotating or night work, shift work cannot and must not be a discriminatory criterion for selecting workers. Particularly, for female workers, more stressful living conditions can arise in relation to time pressures caused by the conflict between irregular working hours and habitual domestic commitments, especially for those women who are married and with children. Conversely, it may be the specific family conditions and/or economic needs that force several women to accept shift or night work. However, it is clear that there is no optimal or best shift pattern, so each shift scheme must be planned and adopted, taking into account the specific working conditions, the peculiar requirements of the tasks, and the particular individual and social characteristics of the workers. The occupational physician should evaluate individual health conditions, which could be related to or aggravated by shift work, to exempt workers from shift work or at least from the night shifts. It is also necessary that helpful information and suggestions should be given to workers on how to best cope with shift and night work, particularly concerning sleep, diet, stress control and good physical health.

Regarding the organization of work schedules, it is advisable to reduce night work by adopting rapid rotation schemes to limit the number of consecutive night shifts as much as possible, reducing the interference on circadian rhythms and sleep. In fact, it is suggested to prefer the rotation of shifts in ‘phase delay’ (Morning/Afternoon/Night), which supports the natural biological circadian rhythms, interspersed by at least 11 h intervals between one shift and the next, in order to allow improved recovery from any sleep loss and fatigue.

The occupational physician can also implement health promotion programs targeting the primary individual risk factors, promoting healthy lifestyle behaviours, for example supporting the introduction of a Mediterranean diet, that has been shown to be associated with a lower risk of BC incidence in women (94,95). The typical Mediterranean diet nutrients have shown a positive influence on the expression of inflammatory biomarkers, oxidative stress, DNA damage and genetic modifications, all aspects that can affect BC outcomes (96,97). Moreover, lifestyle modifications can positively impact BC survival, whose lower health-related quality of life negatively affects treatment compliance and disease outcomes (98).

Occupational physicians should encourage BC screening programs in female workers at risk of BC. It is well established that inclusion into mammography screening programs can result in earlier detection, showing a decrease in the rate of mastectomies, favouring breast conservation surgery. Therefore, BC screening programs are associated with re-employment; in fact, an early diagnosis is frequently followed by a more efficient recovery and improved ability to work. After BC curative treatment, the assessment of a patient's ability to return to work should consider the following: Clinical outcomes, lifestyle and occupational variables. After the sick leave period, employer support to simplify the employee rehabilitation has been associated with a positive return to work experience. A rehabilitation program that combines occupational counselling, physical workout programs and physiotherapy during chemotherapy resulted in an increased return rate to work, improved quality of life and better ability to work (99). In this setting, the role of occupational physicians is crucial in informing workers on the benefits of rehabilitation plans, healthy lifestyles and assistances guaranteed by the law. A virtuous occupational physician should collaborate with the employer to adjust individual risk assessment and optimize tailored calibration of work tasks (Fig. 1).

The current review focused on the contribution of the occupational physician to the prevention and management of BC in the workplace, with a brief overview of the main individual, environmental and occupational risk factors associated with BC, which may have synergistic effects towards the susceptibility, development and progression of BC.

The overall examination of the reviewed contributions does not allow to exclude that exposure to shift and night work is related to an increased risk of developing BC; moreover, it leads to the hypothesis that this relationship is supported by both a theoretical background and possible pathogenetic mechanisms.

Though further studies are needed to establish a causal link, this review suggests introduction of a novel approach to management, including screening tools in the workplace, especially targeting those workers with greater exposure to shift or night work.

In this context, the role of the occupational physician is crucial in primary prevention, health promotion and in the return to work process. In particular, this return to work phase should take into consideration a multidisciplinary approach, involving employers adopting working features tailored on the specific worker's conditions.