Breast Cancer Unit

Breast Cancer Unit

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

Among all breast tumors, around 90-95% are sporadic cases, and only 5-10% of cases have an associated hereditary component.

Although what causes the development of sporadic breast tumors is unknown, multiple risk factors that favor their development have been identified, among which are age and sex, reproductive factors, endogenous and exogenous sex hormones, genetic susceptibility and lifestyle (diet, physical exercise, obesity, environmental pollution and ionizing radiation).

There are different genes that have been associated with a family predisposition to developing breast cancer. The most well-known genes are BRCA1 and BRCA2, although in recent years, other genes that also made up part of the group denominated as hereditary cancer genes have been identified.

The study of these genes is carried out using blood samples from the patient and is indicated in the following situations:

  • Breast cancer diagnosed at an age under 35.
  • Breast cancer diagnosed at an age below 40, if it is bilateral (meaning it affects both mammary glands) or there is no family history.
  • Triple-negative subtype of breast cancer at an age under 50.
  • Breast cancer diagnosed in a male.
  • Association of breast and/or ovarian cancer in various members of the family.

Breast cancer screening

As mentioned earlier, the establishment of screening programs has helped reduce the mortality of breast cancer since it allows it to diagnose the illness in its initial stages.

The current U.S. Preventive Services Task Force recommendations for breast cancer screening are:

  • Perform a mammogram every two years on women between fifty and seventy-four years old.
  • There is no well-established benefit to screening women older than seventy-five years of age.
  • There is no need for breast cancer screening using mammograms for women between forty and forty-nine, and any of these procedures in this age group should be assessed on an individual basis.

The currently available evidence is not sufficient to recommend other exams in addition to the mammogram for women under forty years old.

The recommendations for women between forty and forty-nine years old, as well as how often the mammogram is performed, have led to significant controversy.

That is why it may happen that these general recommendations are modified for specific geographic areas, with one mammogram per year from forty years old on as the most frequent alternative employed.

On the other hand, several studies appear to support the alternating between a mammogram and a breast MRI every six months in women who have been diagnosed with a mutation in the BRCA1 or BRCA2 genes since it reduces the number of late-stage diagnoses of breast cancer. However, the use of breast MRIs outside of this group of patients is not recommended.

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

Breast cancer is a heterogeneous disease and there exist different types of breast cancer. In summary, we can highlight two large groups:

  • Precursor lesions (lobular neoplasia and intraductal or ductal carcinoma in situ).
  • Invasive (or infiltrating) carcinomas.

With regard to precursor lesions, we must focus on the intraductal or ductal carcinoma in situ, which in a very general way, represents the previous step to developing an invasive or infiltrating breast carcinoma.

In general, they do not cause any symptoms and usually manifest in the form of microcalcifications shown in mammograms.

In situ carcinomas do not cause any affectation of the locoregional lymph nodes or distance metastasis, and their treatment is based in surgery and radiotherapy. Chemotherapy is never indicated.

Within the category of invasive or infiltrating carcinomas, the invasive carcinoma of no special type (formerly called the infiltrating ductal carcinoma) stands out as the most frequent variant with 70-80 % of the total number of diagnosed cases (followed by a huge margin by the second most common form, invasive lobular carcinoma, with 5-10% of all invasive breast tumors).

Finally, any invasive or infiltrating breast carcinoma can be classified into three large subtypes:

  • Hormone-positive tumors, which express hormone receptors.
  • HER2-positive tumors, which express the HER-2 receptors.
  • Triple-negative tumors, which don’t express neither hormone receptors or HER-2 receptors.

Prognostic factors

There are multiple prognostic factors that are fundamental when establishing a prognosis and determining the treatment of a patient with breast cancer. Among these, there are:

  • Axillary lymphatic invasion.
  • Tumor size.
  • Histological type.
  • Histological degree.
  • Tumoral lymphovascular invasion.
  • Hormone receptor status.
  • Receptor status.
  • Ki-67 proliferative index.

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.

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