Breast cancer is the most common cancer in women. It accounts for more than one-third of all new cases of cancer in women.
Each breast contains a mammary gland, itself composed of fifteen to twenty lobules and channels, as well as supporting tissue that contains vessels, lymphatic channels, and fat. The role of the lobules is to produce milk during breastfeeding and that of the canals to transport that milk to the nipple.
The mammary gland develops and functions under the influence of sex hormones made by the ovaries. These hormones are estrogens, which allow in particular the development of the breasts at the time of puberty and throughout the pregnancy, as well as the progesterone which plays a role in the differentiation of the cells of the breast and on the menstrual cycle, by preparing for example the uterus to a possible pregnancy.
Breast cells sometimes undergo changes that make their growth pattern or behavior abnormal. These changes may result in benign breast disease, such as atypical hyperplasia or breast cysts, or, more rarely, changes in the breast cells that cause breast cancer.
Breast cancer is most commonly found in the cells lining the ducts carrying milk from the glands to the nipple. This type of breast cancer is called “ductal carcinoma”. Cancer can also form in the cells of the milk-producing glands (grouped into lobules): this type of cancer is called “lobular carcinoma”.
These two cancers (ductal and lobular carcinomas) may be “in situ”, that is, they will remain confined to their original location and not invade neighboring tissues. They can also be “invasive”, that is to say that they spread in neighboring tissues.
Other types of less frequent breast cancers can also be observed: inflammatory breast cancer, triple-negative breast cancer, basal type breast cancer and, very rarely, sarcoma.
The different types of breast cancer
- Benign tumors have well-defined contours. They have a slow growth and remain localized in the tissue or organ in which they appeared: they do not lead to metastases in other areas of the body. Benign tumors are composed of cells that resemble normal breast tissue cells. They are described “well-differentiated”.
- Malignant tumors have contours most often poorly defined. Some, however, are quite limited and can then delay the diagnosis of cancer being considered as benign. The cancerous cells that make up malignant tumors have various abnormalities compared to normal cells: different shape and size, irregular contours. We speak of “undifferentiated cells” because they have lost their original characteristics. Malignant tumors tend to invade neighboring tissues. They can also cause metastases, that is, a new tumor in another area of the body called a “secondary tumor.” The latter is linked to the migration of cancer cells that escape from the primary tumor and will colonize other organs to form a metastasis.
- Most adenocarcinomas develop in the upper outer part of the breast. The most common type of malignant breast tumor is “adenocarcinoma.” There are two main types of adenocarcinoma: “ductal carcinoma” that originates in the lining of the breast ducts, or “lobular carcinoma” that originates in the milk-producing glands (lobules) of the breast.
- The ductal carcinomas and lobular carcinomas are classified as “non-invasive” (“in situ”), that is, they are confined (no spread beyond their location origin and no invasion of surrounding tissues), or “infiltranting”, that is, they have spread beyond their original location into neighboring tissues.
Symptoms of breast cancer
- The most common early signs of breast cancer are related to the presence of an abnormal cluster of cells in the breast.
- The most common early sign of breast cancer is the discovery of a ball or mass in a breast. It is usually the woman herself who discovers this mass, but it is sometimes observed during a screening mammogram even before it can be felt by touch. The mass is constantly present, identical whatever the period of the menstrual cycle. It is usually tender, but not painful, hard, irregularly shaped, and sometimes attached to the skin or chest wall.
- There may be changes in the appearance of the breast. The breast can deform and lose its shape, wrinkles can appear. The skin of the breast can become padded (and take the appearance of an “orange peel”) or wrinkled.
- The skin of the breast may be red, ulcerated, covered with crusts. Nipple changes may also suggest breast cancer. The nipple can point inwards (while usually it is directed outwards). A single nipple discharge may be a sign of breast cancer, especially if it occurs without nipple compression and if it contains blood or if the fluid is greenish. The formation of crusts or ulcers or peeling skin on the nipple may be a sign of a rare type of breast cancer such as nipple Paget’s disease.
- Redness, swelling and significant heat in the breast may be signs of inflammatory breast cancer. Itching of a breast or nipple may be a sign of inflammatory breast cancer.
- Late signs occur when the cancerous tumor grows or spreads to other parts of the body.
- The presence of small hard masses in the armpit may mean that breast cancer has spread to the axillary lymph nodes.
- The spread of cancer cells can happen at a distance to other organs: bone pain, nausea, loss of appetite, weight loss, jaundice (yellowing of the skin and whites of the eyes with dark yellow urine), accumulation of fluid around the lungs (pleural effusion) with shortness of breath and cough, headache.
Can men have breast cancer?
- Breast cancer, like the name indicate, appears in breast tissue and men, like women, do have breast tissue. Thus, even if their breasts are less developed, they too can have breast cancer.
- Breast cancer is rare in men: less than 1% of all breast cancers affect men.
- The risk of developing breast cancer for a man increases with age. Breast cancer is more frequently diagnosed in men over 60 years old.
- Other known risk factors are: family history of breast cancer, genetic predisposition (BRCA2), Klinefelter syndrome, radiation exposure (chest radiotherapy), or cirrhosis of the liver.
- Although the signs of cancer, the course of the disease and the management of invasive ductal carcinoma are almost identical in men and women, there are some differences. Most men with breast cancer have “infiltrating ductal carcinoma” and other types of breast cancer are very rare. Breast cancer in men is treated like that of the postmenopausal woman, where the woman’s ovaries stop producing estrogen.
Risk factors of breast cancer
There are several factors that influence the risk of breast cancer: we talk about risk factors, although there are still uncertainties about the degree of involvement of these factors.
It must be noted that a person who has one or more risk factors may never develop cancer. Conversely, a person with no risk factor may develop this cancer.
Apart from sex (more than 99% of breast cancers affect women), the four main risk factors for breast cancer are age, personal history (in the same breast or in the contralateral breast) and family history ( mother, sister or daughter) of breast cancer and genetic predispositions to breast cancer (BRCA1 and BRCA2 or rare genetic mutations).
Other factors that have been identified include exposure of the body to estrogen-like hormones (early menses and late menopause, prolonged hormone replacement therapy beyond 5 years), exposure to ionizing radiation (chest radiotherapy for Hodgkin lymphoma before the age of 15), overweight, and the consumption of tobacco or alcohol.
Diagnosing breast cancer
Screening for breast cancer is very important because it can diagnose breast cancer at an early stage where the treatment is very effective.
Self-examination should be learned and practiced regularly by all women to monitor their breasts.
A doctor must be contacted upon the appearance of a lump regardless of its type. The doctor will confirm or deny the presence of cancer or a benign tumor.
When a breast cancer is discovered, during a screening test or when a woman already has obvious signs of cancer, several examinations must be carried out knowing that it is the pathological examination of the tissues taken from the breast tumor that will establish the diagnosis of cancer.
In order to make the diagnosis and plan the management strategy, the doctor needs a lot of information, hence a detailed interview, and first of all the symptoms the woman complains about, the risk factors and the medical history that she may have had in the past.
In particular, the doctor will ask if the woman has noticed an increase in the size of the breast ball. The medical history of the immediate family (grandparents, parents, siblings) is also useful in making a diagnosis and looking for a possible specific risk factor. If a familial form of cancer is suspected, an oncogenetic consultation can be proposed. The presence of one or more associated diseases as well as ongoing treatments should also be reported.
After this interview, the doctor will conduct a clinical examination. The latter consists in carrying out a detailed examination of the breasts.
If the abnormality is palpable, the doctor will evaluate its size (always correlated with the size of the breast), the mobility of the tumor (the doctor then will look if the tumor moves under the skin or if it is attached to the wall of the chest or to the skin), its location (which is necessary for the choice of treatments), the appearance of the skin, the shape of the nipple and areola (deformity, retraction, ulceration of the nipple or areola).
These changes are sometimes accompanied by a flow at the nipple that will be sought. The doctor will also look for abnormal ganglia by palpating the different places where they can be (mainly in the armpit). The underarm examination is therefore indispensable and an integral part of the examination. The search for signs of extension of the disease at a distance from the diseased breast will also be put in place by the doctor (bone pain, examination of the liver and lungs …).
The doctor will also ask for tests to clarify the tumor diagnosis and possibly direct the biopsy, first with a “mammogram”. A mammogram is a specific x-ray of the breasts and can be performed either as part of a breast cancer screening (mammography screening), or in the presence of symptoms (diagnostic mammogram). It makes it possible to obtain images of the interior of the breast using X-rays and thus to detect possible anomalies.
When breast density does not provide a quality mammogram, as in some young women, the doctor can then complete the mammogram with an ultrasound. Breast ultrasound uses ultrasound to produce images of the breast interior. Breast ultrasound is often performed in addition to a mammogram. It is useful for seeing the liquid or solid nature of the nodules palpated or discovered on the mammogram.
Treating breast cancer
Different types of treatments can be used to treat breast cancer: surgery, radiotherapy, hormone therapy, chemotherapy and targeted therapies… but sometimes only one type of treatment is enough.
In other cases, a combination of treatments will be needed to better eradicate the disease. For example, one may undergo surgery and then complete the treatment with chemotherapy or radiotherapy.
The choice of treatments is individualized and adapted to the situation of each woman. Several doctors of different specialties (gynecologists, oncologists, surgeons, radiation therapists) meet in “multidisciplinary consultation meeting” to discuss the best possible strategy based on “recommendations of good practices”, which are established by a panel of experts from controlled and validated studies.
The decisions for choice of treatment protocols in breast cancer are based on the stage of breast cancer, hormonal status and possible menopause, the possible presence of hormone receptors for cancer, the HER2 status of cancer, the state of the health of the woman and her susceptibility to certain treatments.
- In most cases, the woman is allowed to choose the type of breast surgery she prefers: breast-conserving surgery followed by radiation therapy or surgical removal of the breast (“modified radical mastectomy”). Other surgical procedures may be required such as axillary lymph node dissection or sentinel node biopsy.
- External radiotherapy is offered after conservative breast surgery and sometimes after mastectomy.
- Chemotherapy is offered in cases of early-stage diagnosed breast cancer that has a high risk of recurrence or in case of locally advanced, advanced or recurrent breast cancer. It may include a combination of drugs or the administration of a single drug depending on the stage of breast cancer. Most breast cancers are treated with “anthracyclines”, a “taxane” or both types of drugs.
- “Targeted treatments or therapies” are drugs that block specific mechanisms of cancer cells. The type of biologic drug proposed depends on the HER2 status of breast cancer. Colony-stimulating factors can be proposed to mitigate the side effects of chemotherapy. In women with BRCA1 or 2 abnormalities, new molecules may be administered in addition to other treatments, anti-PARP, or maintenance therapy.
- Hormone therapy is proposed for breast cancer with hormone receptors that are positive (ER +, PR + or both) at the early stage and whose risk of recurrence is low or locally advanced, advanced or recurrent. The type of hormone therapy proposed depends on menopause. Anti-CDK 4/6 are molecules that bring new hope to HER2 + metastatic breast cancer.
- Bisphosphonates are suggested to prevent or treat bone metastases.
- It is important to have regular follow-up visits, especially during the first 5 years after treatment, to possibly readjust the treatment.
Ductal carcinoma in situ
Carcinoma is called “in situ” when cancer cells are present only in the breast ducts (“DCIS” for ductal carcinoma in situ) or breast lobules (“CLIS” for lobular carcinoma in situ).
The treatment of ductal carcinoma in situ (“DCIS”) is based primarily on a “locoregional treatment” that is, a conservative breast surgery (“lumpectomy”) followed by radiotherapy or surgery. non-conservative breast (“mastectomy”).
Breast-conserving surgery involves removing the tumor and a small amount of surrounding tissue to retain most of the breast. Mastectomy consists of removing in its entirety the breast in which the tumor is located.
Depending on the case, the intervention is accompanied or not by an excision of the sentinel lymph node.
Management of lobular cancers in situ (“CLIS”) is usually based on regular monitoring.
In some cases, a surgical biopsy or excision may be proposed.
Non-metastatic infiltrative breast cancer treatment?
Breast cancer is said to be “infiltrating” when cancer cells have reached the tissues surrounding the lobules or ducts where the cancer originally originated.
The treatment of invasive breast cancer relies primarily on locoregional treatment, ie, conservative breast surgery (“partial mastectomy”) including lymph node surgery (removal of the sentinel lymph node or lymph node dissection), supplemented by radiotherapy, which is non-conservative breast surgery (“mastectomy”), including lymph node surgery (removal of the sentinel lymph node or ganglion dissection) and, if necessary, supplemented by radiotherapy.
This main treatment can be completed depending on the presence or absence of risk factors for recurrence, that is to say, characteristics of the cancer that increase its risk of recurrence after locoregional treatment: the size of the tumor, its grade (its degree of aggressiveness), the involvement of one or more lymph nodes, the non-hormone dependent nature of the tumor, the overexpression of the HER2 protein.
In women with hormone-free breast cancer without the HER2 receptor or affected lymph node (50% of cancers are), performing a test called Oncotype DX Breast Recurrence Score or TAILORx, could avoid chemotherapy and be content with hormone therapy after surgery. Integrating this tool could reduce the need for chemotherapy in women with breast cancer by 70%.
More specifically, this tool makes it possible to assign a genetic recurrence score (SR) of 0 to 100 by analyzing the abnormalities that can relate to 21 genes of the breast tumor. In patients who have a score of 0 to 10 for example, doctors no longer perform chemotherapy in addition to hormone therapy. On the other hand, in those with a score of 26 to 100, chemotherapy is systematic.
The question, therefore, arose for women with an intermediate score of between 11 and 25. However, this score could also help identify those who could benefit from more effective anti-estrogen therapy. In a new analysis presented at ASCO 2019, it is clear that women aged 50 or younger, with a recurrence score between 16 and 20 and at low clinical risk, do not require chemotherapy.
In addition, integration of the recurrence score with clinical risk information can identify premenopausal women with higher clinical risk who may benefit from the suppression of ovarian function and anti-estrogen therapy.
In the presence of risk factors for recurrence, doctors may discuss the need to carry out complementary treatments:
- In case of conservative surgery: radiotherapy of the mammary gland with an additional dose that can be performed on the tumor bed according to age, or radiotherapy of ganglionic areas.
- In case of non-conservative surgery: radiotherapy of the chest wall and radiotherapy of ganglionic areas.
- Whatever the surgery: chemotherapy, possibly associated with targeted therapy if the tumor is HER2 positive and hormone therapy if the tumor is “hormone-sensitive”.
- In the non-menopausal HR + / HER- young woman, an anti-CDK 4/6 antibody will make it possible to increase by one third the survival rate of breast cancer at an advanced stage.
- In all cases, the goal is to limit the risk of recurrence and maximize the chances of recovery.
- In some cases, such as an inflammatory cancer or when the tumor is too large to be operated immediately, the surgical procedure may be preceded by a medical treatment called “neo-adjuvant” (chemotherapy or hormonotherapy in case of a hormone-sensitive tumor).
Metastatic breast cancer treatment
Metastatic breast cancer is a cancer that is associated with distant metastases from the initial tumor. Metastases are tumors formed from cancer cells that have become detached from the first breast tumor (called “primitive”) and have migrated through the lymphatic vessels or blood vessels to another part of the body (bones, lungs, liver most frequently) (so-called “secondary” tumor).
The main treatment for metastatic breast cancer is a combination of chemotherapy, possibly targeted therapy, and / or hormone therapy when the tumor is hormone-sensitive.
Anti-CDK 4/6 molecules are a clear improvement in survival in metastatic HER2 + breast cancer
In some situations, locoregional treatment such as surgery and / or tumor radiotherapy or metastasis is associated with drug-based treatment.
Complications of breast cancer treatment
The swelling of the breast, armpit or arm immediately after surgery is a normal phenomenon that disappears in a few weeks. But a number of complications can occur at a distance from breast cancer treatment.
- Arm lymphedema is a chronic form of arm swelling that occurs when lymph accumulates in the soft tissues of the arm. Lymphedema may occur immediately after surgery or remotely, months or years after breast cancer treatment. It usually appears when one of the lymph nodes has been removed from the armpit area. Women who have undergone “axillary lymph node dissection” are more likely to develop lymphedema. Women who have had a sentinel lymph node biopsy have a lower risk of lymphedema because fewer lymph nodes have been removed. It is also possible that lymphedema develops after radiotherapy of the armpit, causing scarring or blockage that may slow the circulation of the lymph. Lymphedema can also be caused by the spread of cancer to the lymph nodes.
- Many women experience pain after breast cancer surgery. In most cases, this pain disappears on its own. Post-mastectomy syndrome is characterized by nerve pain of neurological origin that occurs after breast surgery and persists for more than 3 months. Post-mastectomy syndrome is more common in women who have had a mastectomy, but it can also occur in women who have had an axillary lymph node dissection or breast-conserving surgery. Younger women and women who are overweight have an increased risk of post-mastectomy syndrome. Post-mastectomy syndrome can be caused by nerve lesions of the breast and armpit during surgery or the development of scar tissue around the remaining nerves. Women may also experience chest, armpit and arm pain on the side of the surgery, such as a burning sensation or continuous stabbing, and sharp pain, or simple numbness. Post-mastectomy syndrome treatment options may include anti-pain medications, anti-inflammatories, opioid analgesics, neuralgic pain medications, transcutaneous neurostimulation, massage, or even the application of capsaicin cream.
- Early menopause may be caused by breast cancer treatment. Menopause usually occurs when a woman gets older, usually in her early fifties. The menopause is caused by the decrease in the level of hormones secreted by the ovaries, mainly estrogen and progesterone. Menstruation becomes irregular until the amount of estrogen becomes so low that it stop completely. Some chemotherapies used to treat breast cancer, such as cyclophosphamide, may block the functioning of the ovaries, particularly in older women who are approaching the age of natural menopause. In younger women, menstruation may re-appear after chemotherapy, but it can take up to a year.
- Hormonal therapy for breast cancer (anti-aromatase) may cause signs of menopause, such as changes in menstruation and hot flashes, but it does not cause real menopause since the interruption of menstruation is reversible if discontinuation occurs before the natural age of menopause.
- Women treated for breast cancer with hormone therapy may have an increased risk of osteoporosis due to early menopause. This is characterized by a loss of bone mass (density) and the deterioration of bone tissue. The bones become fragile and can break easily. Osteopenia is a loss of bone mass that is not as severe as for osteoporosis. Decreased estrogen levels are the most common cause of osteopenia or osteoporosis and are related to stopping ovarian function or hormone therapy. These hormone therapies include aromatase inhibitors in women after menopause or ovarian suppression (through surgery or medication) in premenopausal women. Tamoxifen does not reduce the amount of estrogen in the body and can protect bones in older menopausal women by acting as a lower form of estrogen. However, tamoxifen reduces bone mass and can cause osteopenia in premenopausal women.
- Other risk factors increase the likelihood that a woman will one day develop osteoporosis, including aging (women over 65 years of age are at increased risk), low calcium and vitamin D intake, smoking, lack of physical activity and exercise. A woman with breast cancer along with these risk factors has a greater possibility of developing osteoporosis.
- Axillary Web Syndrome is a problem that can occur as a result of breast surgery. These cords can go down the arm and extend beyond the elbow, up to the wrist. The treatment may include daily stretching and range of motion exercises. In most cases, the cords disappear on their own.
- A loss of self-esteem is often reported. Body image, that is, the way we perceive our own body, is often changed because of the changes the body undergoes because of cancer or its treatments. Some women may feel less feminine because they have no breast or hair loss. These feelings can become worrying and cause distress or depression. Some of these changes are temporary, others take a long time and some are permanent. Group and individual support programs can help women cope with issues related to changes in self-esteem and body image.
- Younger women may be worried about their fertility and ability to have children after treatment. Breast cancer surgery and breast radiotherapy do not affect a woman’s fertility, which is not the case with chemotherapy and hormone therapy. Chemotherapy can damage the ovaries and cause definitive menopause, which is the cessation of estrogen production by the ovaries, while hormone therapy can cause estrogen secretion to stop during treatment from 2 to 5 years.
If detected at an early stage, breast cancer can be treated in 9 out of 10 cases. The screening tests aim to find breast cancer as early as possible and before any extension of the disease. When breast cancer is detected and treated at an early stage, the chances of successful treatment are much better.