Breast cancer is the most frequent malignant tumor among women, and has shown a growing rate of incidence in the last few years. This is likely due to multiple factors, among which stand out the implementation of population screening programs and changes in nutritional and reproductive habits.

However, at the same time, the mortality of breast cancer has decreased thanks to the progressive advancements in oncological treatments, more knowledge about the biology of tumors and the establishment of early detection programs with mammograms that allow an earlier diagnosis of the illness and, therefore, an approach during the initial stages of the disease with higher rates of the disease being cured.

Nevertheless, breast cancer remains in first place for cancer mortality among females. Despite there being no national tumor register system in Spain to provide precise rates for the disease, it is estimated that 32,953 cases of breast disease were diagnosed in Spain in 2020, amounting to 12% of all the tumors diagnosed in women. This is why it is an important public health issue for the female sex.

Risk factors

Breast cancer screening

Clinical manifestations

The symptoms of breast cancer vary both depending on its extension and its location within the breast, as well as whether or not there is distant metastasis.

It was initially thought that after a variable period of growth within the mammary gland, the primary tumor then invaded the locoregional lymph nodes before finally spreading through the bloodstream to more distal organs (Halsted Theory).

Today though, it is a well-known fact that breast cancer can develop distant metastasis without a prior affectation of the locoregional lymph nodes (the Hellman’s Spectrum Theory).

The initial stages of breast cancer are generally asymptomatic and are primarily detected through changes in mammograms and/or the presence of a palpable tumor in the breast. The principal locoregional symptoms and signs of the illness are:

Appearance of a nodule or tumor mass: This is the most frequent and significant clinical discovery. They tend to be painless (they cause no pain) and while most nodules are not malignant, they must all be properly assessed. A hard nodule that grows over time and is connected to the skin or in a fixed point is highly suspicious for malignancy. On the other hand, a soft, mobile nodule that does not grow over time or is not at a fixed point is usually benign. Among these stand out breast cysts and fibroadenomas.

Palpation of an axillary lymph node: Sometimes, it is the first symptom, although a full breast exam is necessarily routine. This discovery must be considered carefully since everyone has lymph nodes in the armpit, and it can even be easy to confuse a benign non-node lesion with a lymph node in that location. Nevertheless, there is the possibility that breast cancer appears exclusively in the form of an axillary lymph node without the primary tumor being evident within the breast.

Thelorrhagia or discharge from the nipple: It is important to know whether this is happening in one or both breasts, in a single duct or several ducts, as well as the characteristics of the liquid secreted. A breast tumor must be suspected when the discharge is only from one breast or only from a single orifice and bloody in appearance. In these patients, the study is carried out using cytology (by taking a sample) of the secretion and sometimes, by performing a galactography, which is an X-ray of the milk duct of the mammary glands.

Nipple inversion or retraction: Sometimes this can be a variation of what is normal, even in patients who initially have a normal nipple and then later it retracts, it may be the first sign of breast cancer and must always be assessed. The presence of eczema on the nipple should make us suspect the possibility of Paget’s disease, which is a particular variation of breast cancer.

Skin changes: “Orange peel skin” with enlarged pores, the retraction of skin or dimples, signs of inflammation and/or ulcers must always alert us to the existence of a breast malignant process. In the presence of these findings, a differential diagnosis should be made with skin diseases of the breast or mastitis (inflammation of the breast).

Pain in the breast or mastodynia: This is defined as a pinching feeling, tension or even sharp pain. It is an infrequent symptom in patients diagnosed with breast cancer, except in advanced cases, and should always be differentiated from breast pain produced by other causes, such as, for example, menstrual cycles.

Breast cancer can spread as it develops and metastasize into other organs. Metastasis is when the tumor spreads to a different location than where the tumor had been found until then. As occurs with tumors in other parts of the body, breast cancer tends to show a preference for specific organs, and the main symptoms and signs of the metastasis depend on the organ that is affected.

Diagnosis

Thanks to the establishment of population screening programs and a greater awareness by the female population about the importance of breast self-exams, the majority of breast cancer diagnoses are made in the early stages.

It is fundamental to perform, first and foremost, a detailed physical examination, both of the breast as well as the locoregional lymph nodes in search of suspicious nodules, asymmetries, skin alterations or changes in the complexion of the areola/nipple, and abnormal lymph nodes.

With regard to the complementary examinations, the first test to be done should be a bilateral mammogram (on both mammary glands), which should then be compared whenever possible to the previous mammograms. The most common pathological findings are the appearance of a nodule, an asymmetry in the mammary tissue and the presence of microcalcifications with suspicious characteristics (they are small, irregular, and in cluster formation).

Furthermore, the mammogram report must always specify the BI-RADS (Breast Imaging Reporting and Data System) used to classify the mammographic findings in a standardized manner.

Depending on the results of the mammogram and the findings in the physical examination, a breast ultrasound and/or a breast MRI may be performed. With regard to the use of the breast magnetic resonance imaging, its fundamental objective is to rule out the existence of tumors in the contralateral breast, as well as the presence of other tumor foci in the same breast.

If after the image tests exists the suspicion of a malignant breast tumor, a biopsy must be carried out, preferably with a core needle, in order to confirm the malignant nature of the tumor and to determine the tumor’s characteristics.

After confirming the diagnosis of breast cancer, it must be evaluated whether the axillary lymph nodes are affected, and in this case the recommended test is an axillary ultrasound. If the affection of the lymph nodes is suspected, a fine-needle biopsy must be taken to confirm the suspicion.

Finally, an extension study is performed to rule out the presence of distant metastasis. The tests to be done for this study include: chest X-ray, abdominal ultrasound, chest and abdominal-pelvic computerized axial tomography (CAT), bone scintigraphy, and a positron emission tomography (PET) scan. The choice of one or more of these tests will be based on the degree of suspicion of distant metastasis.

After the entire study has been done, we will be able to perfectly identify the stage of the disease.

Breast cancer is divided into four stages with significant implications on the prognosis and treatment, being the TNM staging system the most widely used at the moment. This system is based on the size of the tumor (T), whether it affects the locoregional lymph nodes (N) and whether distant metastasis is present (M).

Types of breast cancer

Prognostic factors

Treatment

Surgery, radiotherapy, chemotherapy, hormone therapy and more recently molecular target-based antibodies, specifically against the HER-2 receptor, make up the basic pillars of breast cancer treatment at the moment.

These therapies are applied based on different variables such as the stage of the tumor and the tumor’s characteristics.