Breast Cancer

Breast cancer is a disease in which the cells of the breast reproduce abnormally, resulting in the formation of a tumor in the chest. It generally originates in the ducts of the breast (ductal carcinoma) or in the lobules, which are small milk-producing glands (lobular carcinoma). It is the most common cancer in women, although in rare cases (1% of all cases), it can occur in men.

There are many different types of breast cancer depending on its location, origin, behavior, or extent. In most cases, it is a carcinoma, as these tumors originate in the epithelial cells.

Non-invasive or in situ breast cancer: These are lesions with a good prognosis, as the tumor cells have not spread beyond the duct or lobule where the lesion originated. They do not have local or distant invasive capacity.

• Ductal carcinoma in situ (DCIS): The tumor cells have not spread beyond the duct where the lesion originated. It must be surgically treated, as it may evolve into invasive carcinoma.
• Lobular carcinoma in situ (LCIS): The tumor cells have not spread beyond the lobule where the lesion originated. It is not a precancerous lesion; it is simply a "risk marker" for developing breast cancer.

Invasive or infiltrating breast cancer: The tumor extends outside the duct or lobule where the lesion appears.

• Invasive ductal carcinoma (IDC): The tumor cells originate in the milk ducts. It is the most common, both in women and men.
• Invasive lobular carcinoma (ILC): This is the second most common. It originates in the lobules, which are milk-producing glands.
• Inflammatory breast carcinoma: This is a rapidly growing tumor. The breast becomes inflamed, very red, and hot. It is often confused with mastitis, which leads to a delay in diagnosis.
• Paget’s disease of the breast: This is a scaly lesion on the nipple, which is sometimes associated with breast cancer.
• Metastatic breast cancer: This refers to advanced-stage breast cancer with distant organ involvement.

Breast tumors show different characteristics that allow us to classify them, so that an appropriate treatment plan can be devised for each one.

For this, we analyze the grade of the tumor and the immunohistochemical study.

The Histological Grade, which is graded from I to III, informs us about the histological aggressiveness of the tumor. Grade I is the least aggressive, Grade II is intermediate, and Grade III is the most aggressive.

The Immunohistochemical Study typically informs us about:

• Hormonal receptors (estrogen and progesterone): These are positive in 60-65% of cases. Their positivity indicates a good prognosis, as it means the tumor cells retain the characteristics of the original breast cells. It also predicts the response to hormonal therapy.
• HER2/NEU: This is a surface protein that is overexpressed if the gene is amplified. It occurs in 25% of breast tumors and indicates tumor aggressiveness.
• Ki-67: This is an antigen associated with cell proliferation and is expressed as a percentage from 1 to 100%. The higher the Ki-67, the more aggressive the tumor is considered. Tumors with a Ki-67 < 14% have a better prognosis.

Based on all of the above, we can define 4 types of breast cancer:

• Luminal A: This is the phenotype with the best prognosis. These are low-grade tumors, with positive hormonal receptors and low Ki-67. These tumors respond very well to hormonal therapy and less to chemotherapy.
• Luminal B: These are also hormone-dependent tumors, although in some cases, the progesterone receptor is negative, and the Ki-67 is usually higher. They respond to hormonal therapy but are more resistant and have a worse prognosis than Luminal A.
• HER2 phenotype: These are tumors that express HER2/NEU. They can be hormone-dependent or not. These tumors, initially of poor prognosis, are treated with targeted therapies with excellent response and evolution.
• Triple-negative: These are tumors with negative hormonal receptors and HER2 negative. They have a worse prognosis, but it is improving thanks to certain treatments.

Symptoms

In most cases, breast cancer is detected before it is discovered by the patient or doctors, thanks to screening mammography. When signs or symptoms appear, they are usually as follows:

• Palpable lump in the breast or armpit.
• Changes in the shape of the breast, asymmetry.
• Orange peel texture.
• Nipple retraction.
• Nipple discharge.
• Nipple eczema.

Causes

Breast cancer is a multifactorial disease, though we know that the risk increases with age, and it is more common in Caucasian women of higher socioeconomic status, likely due to reproductive habits (fewer children and at older ages) and breastfeeding habits (less breastfeeding) in the Western world. In contrast, in developing countries, where women have many children at a very young age and breastfeed their children for a long time, the breast experiences less estrogenic stimulation (pregnancy and breastfeeding prevent ovulation), which results in lower mutagenic risk in the breast tissue.

Risk Factors

Genetic Factors

BRCA1 and BRCA2 are two genes that protect against the development of breast and ovarian cancer. In cases where mutations in these genes exist, women who carry them have a very high risk of developing breast or ovarian cancer during their lifetime (reaching 85-90%) in some cases. Other genes associated with breast cancer include CHEK2, RAD51, and PALB2.

Family History

A family history of breast cancer (without a known genetic mutation) increases the risk of developing it, up to 1.7 times if there are first-degree relatives affected, and up to 3 times more if the diagnosis was made in premenopausal patients.

Proliferative Breast Disease

Certain conditions diagnosed through breast biopsies increase the risk of developing breast cancer, such as sclerosing adenosis and nodular hyperplasia (1.5-2 times the risk), atypical ductal hyperplasia or atypical lobular hyperplasia (4-5 times), or lobular carcinoma in situ (up to 8 times).

Menstrual and Reproductive Factors

Early menarche, late menopause, and nulliparity or having children later also increase the risk of developing breast cancer. This is due to the "estrogenic insult" on the breast tissue caused by prolonged ovulation, which increases the risk of mutations in breast tissue. For the same reason, breastfeeding protects the breast and appears to decrease the risk of breast cancer.

Alcohol, Diet, Obesity

Moderate alcohol consumption (1-2 glasses per day) seems to slightly increase the risk of breast cancer, as does a diet high in fats. Obese women, who produce more estrogens in peripheral fat due to androgen conversion, also have a higher chance of developing the disease and, once diagnosed, a higher mortality rate (not only due to cardiovascular risk, etc., but also because of an increased risk of recurrence and secondary mortality).

Prevention

Although until recently self-examination for lumps in the breast was recommended, nowadays prevention is based on early detection tests.

Screening campaigns in Spain consist of a mammogram every two years for healthy women between the ages of 50 and 69. However, specialists determine when it is necessary to start screening from the age of 45.

Additionally, it is recommended to avoid alcohol, exercise regularly, and, if possible, avoid hormonal therapies during menopause.

What doctor treats breast cancer?

The management of breast carcinoma requires a multidisciplinary approach, involving many specialists such as radiologists, gynecologists, radiotherapy oncologists, and plastic surgeons, typically led by the medical oncologist, who plans the treatment in a global and consensual manner.