PRECAMA: Molecular Subtypes of Premenopausal Breast Cancer in Latin American Women

Breast cancer (BC) has become a major public health problem in Latin America (LA), as it is the most common form of cancer among women. In Women are more likely to develop BC at younger age, and to be diagnosed at an advanced stage compared to western women. Over the past twenty years, the mortality from BC in LA has also been increasing very rapidly, and is currently the leading cause of cancer mortality among LA women. The large number of incident BC cases among premenopausal women, which is only partly explained by the population age-structure, is therefore of major concern. Little is known on specific risk factors for premenopausal BC in general, and in LA in particular, and risk factors related to diet, obesity and low physical activity play a role on incidence and mortality. Estrogen receptor (ER) and/or Progesterone receptor (PR) expression in breast tumors may differ according to risk factors and to molecular pathological characteristics. There is a lack of specific knowledge on tumor molecular and pathological characteristics of BC in premenopausal women, particularly in lower resource countries where the hormone-dependence status is poorly documented. This has major consequences on cancer treatment and survival.

To improve our understanding of determinants of BC incidence and mortality in young Latin America women and support preventive actions, we implemented an international, population-based multi-center case-control study in LA: the PRECAMA study (Molecular Subtypes of Premenopausal Breast Cancer in Latin American Women (PRECAMA): a multicenter population-based case-control study).

PRECAMA is coordinated by the International Agency for Research on Cancer (IARC), and is conducted within 4 Latin American countries: Mexico, Costa Rica, Colombia and Chile. Major aims of the project are the following:

• To develop a multi-centric population-based case-control study on BC in premenopausal women in several countries in LA with structured collection of individual, clinical, pathological information and biological specimens, according to strictly controlled protocols
• To characterize, in these populations, the subtypes of premenopausal BC on the basis of their molecular and pathological phenotypes
• To improve the identification of specific endogenous/exogenous factors, and disentangle the interplay of these different factors with regard to breast tumor subtypes.
• Provide advanced training, induce a structuring effect on the BC research community in LA and influence the public health agenda regarding the management of BC.

Standardized methods and questionnaires have been developed and implemented as well as standard operating procedures for laboratory activities. Incident primary invasive cases aged 20-45 years are recruited from major cancer hospitals in four large Latin American cities (Mexico City, San Jose, Medellin, and Santiago) prior to any treatments. Controls for the study are selected from the population residing in the same cities for at least 3 years and matched to cases on age (+/- 5 years) and health care institution. For each subject, complete questionnaire data on socio-demographic factors, health history, reproductive history, use of hormones, early risk factors, body silhouette at different ages, physical activity, diet, occupation, environmental risk factors, ethnicity, and family history of cancer are collected. Validated and standardized food frequency questionnaires are administered to gather information on diet. Anthropometry (body weight, standing and sitting height, waist and hip circumferences) are measured according to standardized protocols. Blood and urine samples are also collected for biomarker analyses. For all cases, highly standardized immunohistochemical and molecular analyses are performed to identify BC subtypes.

The results of our study will be of utmost importance to understand the etiology of breast cancer in Latin America countries in epidemiological transition, and would provide important information on the role of modifiable exposures on the disease which may provide important support for breast cancer prevention.

Inclusion criteria

• woman between 20 and 45 years old
• woman less than 3 years older or younger than the case
• living in the area that the study is taking place during the past 3 years
• woman menstruated at least once in the past 12 months
• woman diagnosed with a primary breast cancer by histopathological examination (only for cases)

Exclusion criteria

• woman receiving tumor treatment, such as radiotherapy, chemotherapy or anti-estrogens (for example, tamoxifen) (except treatment for non-melanoma skin cancers)
• woman taking (or has previously taken) any of the following medications in the past 6 months: tamoxifen, Evista (raloxifene), Fareston (toremifene), Aromasin (exemestane), Femara (letrozole), Arimidez (anastrozole) or Megace (megestrol)
• woman suffering from chronic kidney failure
• woman having a pathology that will hinder adequate communication
• woman who is pregnant or nursing
• woman who has been previously diagnosed with a cancer(except for non-melanoma skin cancers)
• any other reason to exclude