Breast cancer

What is breast cancer?

Breast cancer is a malignancy that arises from cells in the mammary gland. Cancer is essentially caused by genetic mutations or changes at the DNA (gene) level. The information contained in DNA determines, among others, the structure of a cell, its functions and interactions with other cells. Changes at the DNA level cause the mutated cell to stop cooperating with other, healthy cells, stop performing its functions and escape the close control of the organism. Being out of control, the mutated cells start growing exponentially to create a tumour, invade and destroy neighbouring tissue and form metastases (develop new foci of cancer away of its original site).

Breast cancer develops from cells that form the mammary gland. The most common forms of BC are invasive ductal carcinoma arising from milk-duct cells and invasive lobular carcinoma arising from lobular cells and forming breast lobules.

Sometimes, breast is found to show changes referred to as in-situ (non-invasive) cancer, such as ductal carcinoma in-situ (DCIS) or situ lobular carcinoma in-situ (LCIS). Those changes are only located within the milk ducts or lobules without invading the neighbouring tissue. While DCIS type changes have the potential of further spreading and development into the invasive form that requires treatment, LCIS changes are considered to be just an indicator of higher risk of breast cancer and, generally, require observation rather than treatment.

Changes of benign nature may also occur in the breast, i.e. nodules that are not capable of invading and destroying surrounding tissue or spreading to other parts of the body. Unfortunately, it take a series of tests, such as mammogram and microscopic examination of sample tissue (biopsy) to recognise whether the change is benign or malignant. Any alarming change in the breast should be verified by medical examination.

Risk of breast cancer

The risk of developing breast cancer within a woman’s lifetime is estimated at approx. 9-12%. That means that one of every ten women will struggle with that disease. In Poland, more than 16,500 BC cases are diagnosed every year, representing the most common cancer type in the female population. The risk of death from breast cancer is estimated at approx. 4%. In Poland, around 5,500 die for that reason every year. Those figures show that a vast majority of patients can be effectively cured of that disease.

Breast cancer occurs very rarely in men, with approx. 120 new cases registered in Poland annually.

Early stage breast cancer may have no symptoms. The only kind of exam that has proved to be reliable in detecting early curable forms of BC is mammography that should be taken every two years by all women aged 50 to 69 [the exam is free, reimbursed by the National Health Fund (NFZ)].

More advanced forms of breast cancer may produce the following symptoms:

• lumps or nodes felt by palpation (touching),
• change in the size, shape or feel of your breast,
• puckering of the skin or nipple,
• skin changes on the nipple and around it,
• discharge from the nipple, especially if bloodstained,
• redness or dimpling of the skin (orange skin symptom),
• widening of breast skin veins,
• ulceration of breast skin,
• increased nodes in the armpit.

BC can only be diagnosed or excluded based on a number of specialised diagnostic tests. The final diagnosis is made after a medical exam that includes palpation (manual check) of the breast and lymph nodes in the armpit, mammogram (a special type of X-ray to assess the structure of the breast), ultrasonography and biopsy that involves the collection of cells from the tumour and their analysis under microscope.

Based on those exams, the stage of the disease is determined and decisions taken on possible further diagnostics and treatment strategy.

The type of further additional exams depends on the stage of cancer, patients general health status and her comorbidities. Decisions concerning further tests and examinations are taken by a team of doctors based on patient’s current clinical situation. That means that not all of the below listed exams need to be carried out.

In most patients, additional exams preceding treatment are limited to blood test, chest X-ray and ultrasonography of the abdominal cavity. In some cases, diagnosis is extended to include computed tomography (CT), positron emission tomography (PET-CT) and bone scintigrahy. Those exams are not performed routinely for each patient, but ordered by a doctor on a case-by-case basis.

The course of an untreated disease depends on biological characteristics of cancer in a given patient. The tumour may either grow slowly or develop to a large size within a few weeks leading to the destruction of the breast, ulceration and necrosis. At an advanced stage, distant metastases may occur in other organs impairing their functions. Untreated BC leads inevitably to death. The median survival time in untreated patients is slightly over 2.5 year since diagnosis. This means that without any treatment, half of BC patients will not survive three years, 18% will survive five years and just 4% will survive ten years.

Treatment, on the other hand, allows a full recovery in a large part of patients if the disease is not advanced or significant lengthening of life in advanced cases. Currently, owing to effective treatment, 80% of patients at stage IIIA survive five years; with a higher stage, IIIB, the five-year survival rate is 45%. If the disease spreads, stage IV, the median survival rate is 18-30 months.

The main contributing factors of breast cancer are female gender and age:

The risk of BC increases from the age of around 35 and the peak incidence is observed between the ages of 50 and 70 years.

In most cases, (approx. 75%), breast cancer has no other known risk factors. In approx. 10-20% patients, in develops on account of inborn mutations. The risk of developing BC increases if there is a family history of the disease, particularly in grade I relatives (parents, siblings, children). The risk is about twice as high with one relative who have had BC, thrice as high with two relatives, and 10 times as high with history of three relatives diagnosed with BC.

Hormonal factors: – long-term hormonal stimulation – higher risk is observed in women who have had their first menstruation early or who’ve had a late menopause (later than at the age of 55 years). Pregnancy and breast feeding reduce the risk. The age at the first full-term pregnancy is of great significance, too. The risk is higher with women who have never given birth who have given birth after the age of 30.

Hormonal contraceptives: The impact of hormonal contraceptives on breast cancer is not fully defined. Formulations that only contain progesterone are not likely to affect the risk of breast cancer, while those containing both progesterone and estrogens may increase it. It is presumed that the risk of BC rises in women who have taken hormonal contraceptives for more than eight years.

Hormone replacement therapy (HRT), a hormonal treatment applied in the climacteric period to mitigate the menopausal symptoms increase the risk of breast Cancer from approx. 6% up to 30% with hormonal therapy continued for over ten years.

Proliferative breast disease: the risk goes up in the case of hyperplastic lesions, such as atypical hyperplasia or LCIS. Intraductal hyperplasia is considered to be a pre-malignant state.

The treatment of breast cancer is of a combined type, meaning it comprises both local treatment – surgery and radiotherapy – and systemic treatment based on chemotherapy, hormonal and biological methods. The basic treatment modality is surgery which, in certain cases, may be a stand-alone method. In most cases, however, surgery is combined with adjuvant therapy, i.e. radiotherapy, and systemic therapy. The final choice of a treatment method depends on many factors, such as clinical stage of cancer (determined according to the size of the tumour, presence or absence of metastases in the lymph nodes or distant metastases), degree of histological malignancy assessed microscopically, presence of sexual receptors in the tumour, presence of HER2 protein, patient’s age.

A surgical procedure is a basic treatment method for BC which, apart from the breast itself, it may cover regional lymph nodes (i.e. those located in the armpit). The treatment involves the removal of a part of (conservative procedure) or the whole breast (amputation). As regards regional lymph nodes, a whole group of them may be dissected (axillary lymphadenectomy) or just one or several sentinel nodes (those located at the closest distance to the tumour). A treatment method is selected individually depending on staging and a number of other clinical and pathological factors. Surgery may involve:

• amastectomy with axillary lymphadenectomy,
• mastectomy with sentinel node biopsy,
• conserving surgery with axillary lymphadenectomy,
• conserving surgery with sentinel node biopsy.

Breast conserving surgery consists of removal of the tumour while sparing healthy surrounding breast tissue. The procedure allows the patient to keep her breast without diminishing the chance for recovery.

Breast conserving therapy is considered for low-stage cases, i.e. when the tumour in the breast is smaller than 3 cm, and the axillary lymph nodes are non-palpable or palpable as isolated and mobile (clinical stage I and ). Conserving procedure is always supplemented with radiotherapy that reduces the risk of the disease recurring in the breast and prolongs survival. Radiotherapy is usually carried out after the wound is healed, i.e. approx. four weeks after surgery.

In the case of more advanced tumours stage, a conservative procedure may be performed after prior chemotherapy (preoperative (non-adjuvant) chemotherapy). Chemotherapy is delivered at intervals of 28 days over 3 – 6 months. In the event of regression (reduction) of the tumour, it is possible to consider conservative treatment combined with sentinel node biopsy or axillary lymphadenectomy. The conserving procedure is followed by adjuvant radiation therapy. If the response to induction treatment is not sufficient, conserving treatment may not be possible and mastectomy is the only option.

Mastectomy is a surgical procedure that involves the removal of the whole breast. There are several types of mastectomy.

Radical mastectomy – is a very extensive procedure that involves the removal of the whole breast along with chest muscles and the whole content of the armpit. Currently, that procedure is not performed routinely.

Modified radical mastectomy involves the removal of the breast with partial content of the armpit without dissecting pectoral muscles. That procedure is used with most women treated with mastectomy.

Simple or total mastectomy involves the removal of the breast with a small piece of the skin without dissecting the axillary lymph nodes.

Radiotherapy is a type of treatment using ionising radiation generated by special machines called accelerators. Ionising radiation is capable of penetrating deeply into tissue and killing cancer cells occur in it. In breast cancer, radiotherapy is mostly used as adjuvant therapy after surgery. Radiation therapy is always applied after a conserving surgical procedure, bay may also be recommended after mastectomy. Nowadays, radiotherapy is actually indicated for almost all patients treated for BC.

Radiotherapy is totally painless. The therapy involves the irradiation of the area of the breast where the tumour was removed or irradiation of the chest wall at the site of the removed breast. If metastases are present in the lymph nodes, the irradiated area also covers the and the infraclavicular and supraclavicular regions.

To protect healthy tissue, prescribed radiation dose is divided into fractions that are delivered through a 10-20 minute procedure once a day for five days a week. Typically, the treatment involves the delivery of 15 to 25 fractions and may, therefore, take from three to five weeks.

Radiotherapy is well tolerated. Adverse effects may appear both during radiotherapy and many months or even years afterwards. The most common side effects are general weakness and skin changes at the irradiated site. Rare side effects: pulmonary or cardiac complications (when the left breast is affected). Detailed list of side effects:

During and immediately after (up to 2-3 months) radiotherapy:

Frequent:

• redness of the skin at the irradiated site
• feeling of dry skin, itching or burning sensation
• peeling of the skin
• feeling of swelling of the irradiated breast
• stinging or pain in the irradiated breast
• swelling of the arm on the irradiated side
• loss of hair in the irradiated area (hair on the head are outside the irradiated area, so it does not fall out)
• dryness in the throat and oesophagus
• pain when swallowing
• general weakness
• fatigue

Rare:

• dry cough
• nausea, vomiting (very rarely)
• pain when swallowing

Long after radiotherapy (more than three months):

Frequent:

• discolouring of the skin at the irradiated site
• visible blood vessels on the skin
• feeling of dry skin
• fibrosis (hardening and shrinking) of the irradiated breast
• fatigue

Rare:

• pneumonia
• lung fibrosis
• persisting shortness of breath, mainly related to effort
• changes in electrocardiogram
• increased risk of heart attack
• necrosis or broken ribs and shoulders
• persisting swelling of the arm on the irradiated side
• pain in the neck and shoulder on the irradiated side

In some BC patients, the disease may spread forming metastases to distant organs. The metastatic potential indicates that breast cancer should be considered a systemic disease that requires a systemic treatment based on chemotherapy, hormonal therapy or biological therapy.

Systemic treatment may be applied both before surgery in order to reduce the mass of the tumour (non-adjuvant treatment), as adjuvant treatment after surgery and radiotherapy and as a primary method in a generalised pathology.

Preoperative treatment (non-adjuvant or inductive) is implemented in advanced cancer cases when, due to the size of tumour, the infiltration to surrounding structures or packages of lymph nodes, it is no longer possible to perform a safe surgery. Such therapy may sometimes be proposed to some patients prior to conserving surgery. Initial systemic treatment prior to surgery is also applied in the event of the disease progressing very fast.

Post-operative treatment (adjuvant treatment) is used to reduce the risk of relapse or generalisation of the disease. The type of adjuvant therapy is determined based on pre-defined course of action and depends on such factors as: the size of tumour, presence of metastases in the lymph nodes, histological structure, presence of sexual hormone receptors in the tumour, hormonal status (pre- or post-menopausal), patient’s age. Currently, most patients qualify for systemic adjuvant therapy.

Generalised disease treatment – if distant metastases are found, the diseases is classified as generalised and requires systemic treatment. With cancer becoming generalised, recovery is no longer possible; however, the progression of the disease may be stopped and the disease treated as a chronic condition. The main objective of such treatment is not to prolong life but to improve its quality.

Systemic treatment is based on chemotherapy, hormonal or biological therapy (monoclonal antibodies).

Chemotherapy uses cytostatics whose main function is to damage rapidly dividing cancer cells. It involves regular administration of medicines, usually intravenously, every 3-4 weeks over approx. 6 months. As cancer cells are similar to constantly dividing normal cells of the bone marrow or gastrointestinal epithelium, chemotherapy may cause some toxic side effects. The most common side effects are that occur during chemotherapy are nausea and vomiting, general weakness and malaise. Some undesired effects can now be effectively prevented and most patients tolerate that form of therapy quite well.

Hormonal therapy – hormonal treatment is carried out in patients who have been found to have steroid hormone receptors in the tumour. Those receptors occur in approx. 70% BC patients. The presence of estrogen and progesterone receptors imply that breast cancer is hormone-dependent and is capable of responding to hormonal stimuli, particularly from estrogens produced by the organism. By binding with receptors in cancer cells, hormones stimulate them to grow and divide. The point of hormonal therapy it to inhibit hormonal stimulation. Depending on patient’s hormonal status, (pre- or post-menopausal), anti-estrogen medicines (tamoxifen) or aromatase enzyme (that transforms estrogen steroid hormones in women women whose hormonal ovarian function has ceased). Hormonal medicines in the form of tablets are used once a day for five days. Additionally, in some patients the ovarian function is stopped by surgical or pharmacological castration.

Biological methods – treatment based on the use of monoclonal antibodies targeted antigen and HER-2 receptor situated on the surface of cancer cells. That receptor is found in approx. 20-30% patients. The inhibition of that receptor by means of antibodies leads to the death of cancer cells. The treatment involves periodical, three-weekly, intravenous administration of the medicine. It takes twelve months.

• Following radiotherapy your body will not become radioactive!
• You do not pose any health threat to your family, including children!

TREATMENT WITH IONISING RADIATION IS ASSOCIATED WITH POSSIBLE SIDE EFFECTS: the most common symptoms being:

local pain, swelling arm on the irradiated side, limited mobility of the shoulder on the irradiated side, skin tightness sensation and skin changes in the form of red to brown spots, itching, burning, exfoliation.

IT IS IMPORTANT NOT TO IGNORE ANY SYMPTOMS, AND REPORT THEM TO A NURSE OR DOCTOR. THOSE SYMPTOMS MAY BE MITIGATED OR ELIMINATED.

When treated with ionising radiation, please, comply with the following instructions:

1. When relaxing, try often to keep your hand up on the treated side (on a wedge).
2. Avoid wearing breast prosthesis or bras (as they can irritate the skin).
3. Often ventilate the irradiated site.
4. Wear loose and airy underwear made of natural fabrics.
5. Do not exert yourself, do not lift heavy loads, especially with the arm on the irradiated side.
6. When feeling short of breath, relax in a sitting position.
7. Drink up to two litres of neutral liquids a day.
8. Avoid food which is too spicy, hot, cold or sour.
9. If you have trouble swallowing, consider changing your diet.
10. Drinking linseed is proved to deliver good results.
11. Wash the irradiated area but very gently.
12. Use soap of acid PH or mild child soap.
13. Dry you skin without rubbing.
14. Don’t wash off the skin markings!

SMOKING AND DRINKING ALCOHOL DURING RADIOTHERAPY REDUCES THE CHANCE FOR RECOVERY FROM CANCER AND INCREASES RADIATION TOXICITY IN THE COURSE OF THERAPY !!!

When treatment is over patients undergo a regular follow-up. Follow-up is aimed to detect local or regional cancer recurrence at an early stage. Active search for symptomless distant metastases if of less relevance, as detecting them through an extended scope of follow-up tests does not affect significantly the effectiveness of treatment and patient’s quality of life. Therefore, routine laboratory and imaging tests, such as CT or ultrasonography, are not recommended. Those exams are only undertaken on strict clinical indications, if cancer recurrence is suspected.

Usually, the pattern of post-treatment follow-up visits is as follows:

• first 2 years – every three months,
• 2-5 after treatment – every six months, then every year. Mammogram every twelve months in the case of a breast conserving surgery, the first mammogram should be performed six months after the procedure.

Additionally, gynaecological exam is recommended every year and, for some patients, densitometric exam every 12-24 months.

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