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BREAST CANCER THERAPY

Various epidemiological studies show that breast cancer represents, in western countries, the most frequent neoplasia in the female sex. In western Europe about one woman on ten develops clinically a mammary carcinoma in the course of her life.

Breast carcinoma represents besides the first cause of death for cancer in the female sex. In women with age among the 35 and the 55 years it constitutes the most important cause of death in absolute, while in women over the 55 years it represents the second cause of death after the cardiovascular illnesses.

These brief epidemiological data underline the importance - in medical practice - of a sufficiently in-depth knowledge of the clinical and therapeutic problems connected to breast cancer management.

This article focus the attention on the therapeutic aspects ( surgery, chemotherapy, radiotherapy, hormonal therapy) of mammary carcinoma.

Therapy of Invasive Breast Cancers with Diameter less than 3 Centimetres

Breast cancers diagnosed in clinical practice are usually malignant tumors of little dimensions ( diameter less than 3 centimetres ).

Invasive breast carcinomas with diameter less than 3 centimetres are treated surgically with a conservative technique, defined quadrantectomy. This surgical procedure was introduced by Umberto Veronesi, at the "Istituto dei Tumori" of Milan, in the seventy years.

The cosmetic result of quadrantectomy is generally excellent. Various clinical studies have besides demonstrated that the long term survival and the percentage of local relapse and distance metastasis are the same in women treated with conservative surgery, followed by local radiotherapy, and in women treated with total mastectomy.

Quadrantectomy consists in a wide resection of the neoplastic nodule plus an ample margin (2-3 centimetres) of healthy parenchyma, so to remove a whole quadrant of the breast, with the corresponding portion of the skin (the skin incision usually begins at the areolar margin) and of the fascia of pectoralis major muscle.

In the cases of retroareolar mammary tumors mastectomy is often preferred to quadrantectomy, because of the poor cosmetic results of a "central quadrantectomy".

Breast reconstruction with silicone prosthesis is usually performed during the surgical procedure of quadrantectomy.

During quadrantectomy a complete dissection of the axillary lymph nodes ( total axillary lymphoadenectomy ) is usually also performed. In the axillary dissection the skin incision is made in continuity with the incision of the mammary exeresis only when the tumor is located in the upper outer quadrant of the breast; in the other cases lymphoadenectomy is performed with a separate incision.

Lymphedema rates of 10 to 25 percent are reported after complete dissection of axillary lymph nodes. An early rehabilitation programme (image A and image B), to be started on the first post-operative day, restores mobility to the arm and shoulder and reduces the incidence of lymphedema, due to progressive sclerosis of the lymphatic vessels of the arm because of lymph stasis .

To avoid the invalidating side effects of the axillary dissection a new conservative surgical technique - defined " sentinel lymph node biopsy" - has been recently introduced in clinical practice for the women with tumors of diameter less than 1 centimetre and therefore with low risk (5-10%) of axillary lymph node metastasis.

Since the metastatic diffusion of breast cancer to the axillary lymph nodes happens in a regular and progressive way - usually without level jump - from the first to the second and then to the third axillary lymph node level, the first or "sentinel" lymph node, that receives lymph from the mammary region containing the neoplasia, is identified and removed with a little surgical incision and then analysed to predict the disease status of the axilla.. To identify the sentinel node, colloid parts of human albumin - labelled with radioactive technetium (99mTc) - are injected into the breast close to the tumor three hours before the surgical intervention; the cutaneous projection of the sentinel node is then revealed by a gamma-ray detector probe.

Various clinical studies demonstrated that histological status of sentinel lymph node accurately predicts the status of the axillary nodes as a whole. In particular, examination of the sentinel lymph node has a good negative predictive value (96-100%).

The histological negativeness of sentinel lymph node during intrasurgical or postsurgical pathological examination is therefore highly predictive of the histological negativeness of all the other axillary lymph nodes and allows to avoid the complete axillary dissection, with the inevitable precocious and late complications related to this surgical procedure. The histological positiveness of the sentinel lymph node is instead a mark of the regional diffusion of the neoplasia and imposes the recourse to the total axillary lymphoadenectomy.

Radiotherapy represents an integral part of conservative treatment. After the intervention of conservative surgery with quadrantectomy and lymphoadenectomy, the residual breast ( but not the axilla, to avoid a damage to vascular and nervous structures ) is irradiated. Radiotherapy after quadrantectomy eliminates occult neoplastic foci in the breast and reduces the risk of local tumoral recurrences, even in consideration of the frequent multicentricity of mammary carcinomas.

The radiotherapeutic treatment should start 30 to 60 days after surgical intervention (but a delay of radiotherapy 6 months after the surgical intervention doesn't increase nevertheless the risk of local recurrences) and is compatible with contemporary administration of adjuvant systemic therapies. It consists in the administration to the breast of a dose of 50-60 Gy in 6 weeks; since 80% of local tumoral recurrences occur in the same quadrant of the original surgery, a radiation boost (15-20 Gy) to the tumoral bed (marked by surgical clips) should always be administered.

Various clinical studies are now evaluating the effects of Intraoperative Radiotherapy (IORT) in the conservative treatment of breast cancer.

IORT is a special radiotherapic technique that uses new dedicated accelerators installed in the operating room, with a positive effect on clinical outcome, quality of life, costs and therapy logistics. A high dose of radiations is administered to the operating field in a single fraction during the intervention of conservative breast surgery, allowing an early radiotherapic treatment, with maximum precision in dose administration, and saving healthy organs from radiations.

After the QUART treatment (Quadrantectomy, Axillary dissection, Radiotherapy ), the further phases of the therapy of mammary carcinoma vary with regard to the pathological and clinical element of greater importance for the prognosis of breast cancer: the presence or the absence of axillary lymph node tumoral involvement.

The 50 percent of the patients with breast carcinoma treated with surgical intervention show a local or distant neoplastic recurrence within the first three years from the intervention if the axillary lymph nodes are positive, and within two years if the number of positive lymph nodes is >10. The presence of axillary lymph node metastasis is so a very important clinical element, suggestive of a more aggressive neoplasia, already sistemically diffused. It suggests therefore the necessity to add to the locoregional therapy (surgery, radiotherapy) a further systemic adjuvant treatment (chemotherapy and/or hormonal therapy).

Tumors with Axillary Limph Node Involvement

The presence of positive axillary lymph nodes (N+) indicates that the tumor has begun a systemic diffusion and is then probable the existence in peripherals organs of metastatic tumoral microfoci, not yet clinically evident. In these cases a locoregional therapy only doesn't secure therefore oncologic radicality. The patients with positive lymph nodes at the histological examination have so to be submitted to a precautionary (adjuvant) systemic chemotherapeutic treatment: adjuvant chemotherapy .

Adjuvant chemotherapy is a post surgical chemotherapy in absence of clinical evidence of peripheral metastatic locations. The follow-up data of 10 and 15 years show that adjuvant chemotherapy determines a constant reduction of the risk of tumoral recurrences and of death of about the 25 percent.

The adjuvant chemotherapy begins usually 2-3 weeks after the surgical intervention and may be administered during the radiotherapic treatment.

The chemotherapic adjuvant regimen most frequently used is still today the combination CMF (cyclophosphamide + metotrexate + fluorouracil), created by Bonadonna at the "Istituto dei Tumori" of Milan in the seventy years, although other combinations containing anthracycline (FAC, fluorouracil, doxorubicin, cyclophosphamide; FEC, fluorouracil, epirubicin, cyclophosphamide; AC, doxorubicin, cyclophosphamide) - administered intermittently at intervals of 3 to 4 weeks - are now often preferred.

The classical CMF has been created with the objective to repeat the success obtained with the MOPP regimen in the therapy of Hodgkin lymphoma; a CMF cycle is constitued by two weeks of treatment and two weeks of interval, before the following cycle. Cyclophosphamide is administered orally in the days from 1 to14, while metotrexate and fluorouracil are administered intravenously in the days 1 and 8, with every cycle repeated every 28 days for a total of 6 cycles.

If histological examination with the assessment of receptor status reveals the positiveness of the neoplastic cells for the estrogenic receptors (ER+) and therefore the hormonosensibility of the tumor, chemotherapy is accompanied by an adjuvant endocrinotherapy

Usually adjuvant endocrinotherapy consists in the administration of tamoxifen, which has an estrogen-antagonist action on breast glandular tissue. Tamoxifen is administered orally at daily doses of 20 mg for a period of 5 years. Tamoxifen may be administered starting few days after the surgical intervention.

Since tamoxifen increases the risk of endometrial cancer, because of a proestrogenic effect on the endometrium, an annual pelvic examination with endovaginal ultrasonography is recommended in patients assuming tamoxifen.

Tumors without Axillary Limph Node Involvement

The negativeness of the axillary lymph nodes for neoplastic infiltration (N-) is considered the most important clinical index of a still localized breast cancer. For this reason, when the histological examination of the surgically removed axillary lymph nodes doesn't reveal the presence of neoplastic cells, the diagnostic and therapeutic iter may be considered finished after the QUART treatment (even if today prevails, however, the tendency to administer to these patients tamoxifen at daily doses of 20 mg for 5 years, when there is a positive estrogen receptor status).

In accordance with the results of the most recent clinical observations and controlled studies, in the group of patients with negativeness of the axillary lymph nodes (N-), generally considered at " good prognosis " compared with patients N+, exists nevertheless a subgroup of women (about 30 percent), with the same high risk of recurrence showed by patients with axyllary lymph node involvement. This group is constituted by women less than 35 years-old and/or with tumoral diameter more than 2 centimetres and/or with histological grade (G) 3 and/or with negative estrogen receptors. This women are today treated in the same way of the patients with involvement of axillary lymph nodes: they are therefore submitted to adjuvant chemotherapy (CMF, FAC, FEC, AC) and, in case of positiveness for estrogen receptors, to adjuvant endocrinotherapy with daily tamoxifene 20 mg orally for five years.

Therapy of Invasive Breast Cancers with Diameter more than 3 Centimetres

The treatment of the breast tumors with diameter more than 3 centimetres consists as first option in a total mastectomy with complete axillary dissection, with or without immediate or delayed reconstruction of the breast with silicone prosthesis or muscolar flaps.

Total mastectomy consists in the removal of the whole breast gland, including the skin, the areola and the nipple. The resection has to be extended down to the fascia of the pectoralis major muscle.

Radiotherapy after total mastectomy is not a routine treatment. Postmastectomy radiotherapy reduces the incidence of local recurrences by 50 to 75 percent, but in most studies it not increased survival. For this reason and because of its potentials side-effects, radiotherapy after mastectomy is performed usually only in patients at high risk for local recurrences (large tumors infiltrating the skin or the chest wall or tumors with many positive axillary nodes).

Postsurgical adjuvant chemotherapy with CMF, FAC, FEC, AC regimens and treatment in ER+ patients with adjuvant endocrinotherapy ( tamoxifen 20 mg daily for 5 years) are usually performed.

To consent even in patients wth larger breast tumors a conservative surgical treatment, a new chemotherapeutic approach - pre-operative or neoadjuvant chemotherapy - has been introduced in clinical practice.

Neoadjuvant chemotherapy is a sistemic therapy given before local surgical intervention, with the aims to reduce the size of the primary neoplasia, in order to make conservative surgery feasible even in women with tumor diameter of 3 cm or more. Many studies demonstrated that pre-operative chemotherapy (with FAC, FEC, CMF regimens, 3-4 cycles; or with more recent combinations with paclitaxel) reduced the requirement for total mastectomy and made possible a conservative surgery with quadrantectomy in a large percentage (90%) of patients, decreasing the size of primary tumor under the 3 centimetres. QUART treatment is followed in these cases by adjuvant chemotherapy and by adjuvant endocrinotherapy (tamoxifen 20 mg daily for five years) in ER+ patients.

Therapy of Locally Advanced Breast Cancer

The term "locally advanced breast cancer" includes tumors of any size with invasion of the breast skin or of the chest wall, and any breast carcinoma with fixed axillary lymphoadenopathy. These tumors have a 5-years survival of 20-30%.

The so called "inflammatory breast carcinoma" is also usually included in this category.

Inflammatory breast cancer is a malignant condition with a rapid appearance and evolution, characterized at histological examination by a diffuse tumoral infiltration of the lymphatic vessels of the breast dermis; clinically the breast appears hard and inflamed, with an erysipelas-like appearance. The 5-years survival of the patients with inflammatory breast carcinoma is of 10% or less.

Some years ago these tumors were considered inoperable and were treated only with a combination of radiotherapy and chemotherapy, without surgery .

Today neoadjuvant chemotherapy plays an increasingly important role in the therapy of locally advanced breast cancer and make often surgery feasible.

Neoadjuvant or primary or pre-operative chemotherapy (FEC 3 or 6 cycles, AC 4 or 6 cycles) is a systemic antineoplastic therapy given before local surgery . In more than 65% of patients the tumors shrink by more than 50% with preoperative chemotherapy. Most previously inoperable breast cancers become operable and often breast-conserving surgery is possible.

Neoadjuvant chemotherapy is followed by surgery, adjuvant chemotherapy, radiotherapy and adjuvant endocrinotherapy with tamoxifen 20 mg for five years.

With this multimodal approach excellent local control is achieved in 75 to 90 % of women with locally advanced breast cancer and about 30% of patients remain free of breast cancer after 10 years.

Therapy of Metastatic Breast Cancer

Metastatic breast cancer represents a pathology to be cured with only palliative finality.

Frequent testing to identify precociously sistemic metastases of breast carcinoma has not modified the clinical course of patients with metastatic disease.

It is mandatory to utilize all available treatments to obtain optimal palliation of symptoms and to prolong survival, with little impairment of the quality of life.

Metastasis of breast cancer occur more frequently in the soft tissues, in the skeleton, in the lungs and in the liver.

The antineoplastic treatment with chemotherapy (first-line treatments with CMF or regimens with anthracycline; second-line and third-line treatments using taxanes, vinorelbin, cisplatin), hormonal therapy (first line therapy with antiestrogens - tamoxifen - ; second-line therapy with LHRH analogues - triptorelin, goserelin, leuprorelin - in premenopausal patients and with aromatase inhibitors - aminoglutethimide, formestan, anastrozol - in postmenopausal women; third -line treatments with progestins - megestrol acetate -; fourth-line treatments with androgens), radiotherapy (for example radiotherapy of cerebral metastasis or irradiation of bone metastasis, added to biphosphonates therapy) and sometimes limited surgery in the most of the cases prolongs survival, induces a temporary partial or complete tumoral regression and improves the quality of life.

The choice of the antineoplastic treatment in patients with metastatic breast carcinoma has to be made on the basis of the knowledge of the clinical and biological data of the neoplasia (in particular the hormone-receptor status), of the age of the women, of the disease-free interval before the appearance of the metastasis and of the number of the metastatic locations (extent of disease).

Hormonal therapy represents the initial treatment of choice in elderly women with estrogen-receptor positive tumors and in women with limited, not symptomatic and not life-threatening disease. Patients who show a respons to one hormonal treatment often respond to a second and then to a third or fourth hormonal intervention, when the previous become ineffective. Many patients may thus benefit from three or four endocrine treatments, with a good quality of life and with little symptoms and limited side effects for many years.

In patients with aggressive and rapidly evolving metastatic tumors, with brief disease-free interval and visceral metastatic locations, or when breast cancer becomes refractory to endocrine therapy, chemotherapic treatment is usually performed with good palliative results.

High dose chemotherapy (antineoplastic drugs given at doses 2 to 20 times as high as standard doses) with reinfusion of autologous hematopoietic stem cells is under clinical evaluation. Several studies, however, show no evidence that such therapy results in any better clinical course than that obtained with standard-dose chemotherapy.

Recent clinical studies show that the addition of trastuzumab - a monoclonal antibody directed against the human epidermal growth factor receptor HER2 (also called ErbB2) - to chemotherapy in patients with metastatic breast diseases that overexpresses HER2 is associated with better responses and longer survival than that obtained with chemotherapic treatment alone. However, cardiotoxicity is a serious complication of therapy with trastuzumab, especially when administered in combination with anthracyclines.

Metastatic breast cancer, especially with involvement of bone, is often characterized by an important pain syndrome that requires an individualized Palliative care, based upon the Cancer Pain Management Guidelines published by the World Health Organization. A correct therapy of cancer pain is effective in relieving pain in approximately 90% of patients with metastatic or terminal breast carcinoma.

The first step of pain treatment (mild to moderate symptoms) requires the use of paracetamol, aspirin or another NSAIDs.

The second step ( pain not well controlled) consists in adding an opioid such as codeine, oxycodone or buprenorphine to the NSAID.

In the third step severe pain is controlled with the oral, subcutaneous, transdermal, spinal use of more potent opioids, such as morphine, fentanyl or methadone.

Therapy of Axillary Metastases without Evidence of Primary Breast Cancer

In presence of axillary metastases without clinical and instrumental evidence of the primary breast tumor (1% of cases of breast cancer) complete axillary dissection represents the treatment of choice.

Mastectomy is usually not performed; radiotherapy of the whole breast (60 Gy) is preferred for the treatment of the occult primary tumor.

Surgery of the axillary lymp nodes and breast irradiation are followed by adjuvant sistemic treatment with CMF (or other chemotherapic regimens) and with tamoxifen.

Therapy of In-Situ Breast Cancers

Lobular carcinoma in situ (LCIS) is usually an anexpected histological finding after a surgical breast intervention.

In presence of a lobular carcinoma in situ a wide resection without axillary dissection is indicated.

If multicentric tumoral foci of LCIS are found, a subcutaneous mastectomy without axillary dissection is the treatment of choice.

Recent sudies demonstrates that tamoxifen reduces the incidence of invasive carcinoma in patients with LCIS.

Intraductal carcinoma in situ (DCIS) is treated with wide resection or quadrantectomy plus radiotherapy on the affected breast. Radiotherapy reduces the incidence of local recurrences in patients with DCIS treated with conservative surgery.

In presence of multicentric tumoral foci of DCIS, subcutaneous mastectomy or total mastectomy, without radiotherapy, are performed.

Axillary dissection is not usually indicated in patients with DCIS.

Tamoxifen (20 mg for five years) reduces the incidence of local recurrences in women with DCIS.

Therapy of Paget's Disease

Paget's disease of the breast is an uncommon pathology, accounting approximately for about 0,5-3% of all breast cancers.

Paget's disease is an intraductal mammary carcinoma extending to the epidermis of the nipple and areola through a lactiferous duct.

Clinical examination shows an eczema-like lesion of the nipple and areola.

Seldom Paget's disease of the breast mimics a melanocytic pathology (pigmented Paget's disease).

The therapy of choice in Paget's disease without an underlying tumor is central quadrantectomy, without axillary dissection, followed by radiotherapic treatment on the affected breast.

If Paget's disease is associated with an underlying tumor (infiltrating carcinoma), an extensive central quadrantectomy with radiotherapy (for superficial nodules smaller than 2,5 cm and centrally located) or a modified radical mastectomy (in other cases), both with axillary lymph nodes dissection, are indicated.

Therapy of Local Recurrences

The appearance of a local recurrence of breast cancer months or years after surgery (clinical evidence of illness relapse at the thoracic wall or at the axilla after total or radical mastectomy, at the residual breast - usually close to the surgical scar - or at the axilla after conservative therapy ) is a frequent event in clinical practice.

The prognostic meaning of local recurrences depends on their extension and location and on biological characteristics of the primitive tumor.

Is generally recognized a better prognosis for the patients with intramammary recurrences ( 50-70% of survival at 5 years ), while in the other cases the local relapses often are the prelude to the appearance of peripheral metastases.

In case of intramammary recurrence after conservative surgery, when it occurs very close to the surgical scar a new limited resection may be considered if the neoplastic lesion is small; all other cases are treated with mastectomy. Axillary lymphoadenectomy has to be done when the sentinel-lymph node technique was previously used with saving of axillary lymph nodes.

Radiotherapy of the breast and of the thoracic wall is not usually performed - unless it was not given after the first conservative surgical intervention - because of the incidence of serious functional and cosmetic side-effects.

When an axillary recurrence occurs, it is surgically treated with the removal of the tumoral mass. If the surgical treatment is not feasible, radiotherapy of the axilla is performed.
In case of thoracic local recurrence after total mastectomy, radiotherapy of the chest wall is the treatment of choice. When the tumoral nodule is single, radiotherapy is preceded by surgical removal of the neoplastic lesion.

Sistemic chemotherapic and/or ormonal treatments follow usually the locoregional therapy, to prevent the occurrence of distant metastases.

Since local recurrences, otherwise than metastases (there is in fact no clinical evidence that earlier detection of breast cancer metastases improves prognosis) , represent often a curable condition, the Follow-up of the patients after the surgical therapy of the primary mammary cancer has to be focused on the breast, the chest wall and the axilla.

Standard follow up consists of physical examination of the patients every six months and mammography once a year.

Therapy of Breast Sarcomas

Breast sarcomas (cystosarcoma phylloides, fibrosarcoma, liposarcoma, non-Hodgkin's lymphoma) represent the 1% of all breast cancers.

Mammography and ecography have a low sensibility in order to establish the sarcomatous nature of a breast nodule; only intraoperative histological examination defines the exact diagnosis of sarcoma.

Breast sarcomas have a hematological (rather than lymphatic) metastatic diffusion.

The treatment of choice in patients with breast sarcomas is total mastectomy, without axillary dissection. A conservative surgical treatment (quadrantectomy or wide breast resection) may be performed when a wide margin (3 centimetres) of healthy surrounding tissue can be removed.

Breast Cancer Therapy in the Elderly Woman

The treatment of breast cancer in women > 70 years of age has to be planned considering the tumoral stage at the time of diagnosis, the general clinical conditions of the patients and the concomitant illnesses.

In presence of operable nodules, the treatment of choice is represented by surgery (quadrantectomy or total mastectomy with axillary lymphoadenectomy), as in women < 70 years of age. When general anaesthesia is not possible for the presence of clinical controindications, lumpectomy (tumorectomy) is usually performed in local anaesthesia.

The choice to administer the post-surgical radiotherapic treatment in elderly patients has to be made individually, considering the risk of local recurrences, the presence of logistic problems and the expectation of life.

As regards the systemic antineoplastic treatment in the elderly patients with breast cancer, hormonal therapy with tamoxifen (20 milligrams orally once a day for 5 years) has to be preferred, even in women with negative estrogenic receptors. Chemotherapy is administered only in selected cases.

Breast Cancer Therapy in Men

Breast cancer may appear even in males; it originates from the mammary glandular buds.

Breast cancers in men represent the 1% of total mammary neoplasias; breast cancers constitute besides the 1% of all male tumors.

The diagnosis of mammary carcinoma is effected even in males using mammography, echography and, if necessary, fine needle biopsy or surgical biopsy .

Male breast presents mammographically as a mass without microcalcifications in 85% of patients and as a mass with microcalcifications in 7% of patients. The location of the mass is retroareolar in 45% of cases and eccentric to the nipple in 55% of cases. On ultrasonographic examination the neoplastic masses are usually ipoechogenic, with irregular contours.

The therapy of breast cancer in males is not much different from that practised in case of female mammary neoplasias.

Total mastectomy (with removal of the whole breast gland, including the surrounding skin, areola and nipple) with total axillary dissection is the treatment of choice.

Surgical treatment is followed by adjuvant chemotherapy ( in particular if axillary lymph nodes are involved), radiotherapy of the thoracic wall (when the tumor is locally advanced ) and hormonal therapy with tamoxifen ( 20 mg once a day, to be continued for five years if the neoplasia results positive to estrogen-receptors and sensitive to the hormonal treatment ).

Breast Cancer Therapy in Pregnant Women

Patients who become pregnant just before or after the diagnosis of a stage I or stage II invasive breast cancer have no increase in mortality compared with controls.

Pregnancy does not have an adverse effect on survival in patients with breast cancer, particularly among patients with local illness.

Pregnant women with breast cancer have, however, an higer rate of abortion (24% compared with 18% in controls).

After a primary treatment for breast cancer in premenopausal patients who desire a child, a new pregnancy has preferably to be postponed until after the fifth disease-free year.

In pregnant women with operable tumors surgical therapy is the same as for non-pregnant patients.

Radiotherapic treatment after conservative surgery (for breast carcinomas with diameter less than 3 centimetres) has to be postponed until after delivery, because of the teratogenic effects of radiations.

When adjuvant chemotherapy is indicated (node postive patients), it may be admnistered in the first trimester if pregnancy is terminated (depending on the wishes of the woman); otherwise chemotherapic treatment has to be postponed until after the fourth month of pregnancy, because of the teratogenic effects of antineoplastic drugs.

When a locally advanced breast carcinoma is diagnosed during the first or second trimester of pregnancy, induced abortion is indicated and chemotherapic treatment has to be administered without delay.

When a locally advanced breast carcinoma is diagnosed during the third trimester of pregnancy, delivery has to be induced early in order to begin rapidly the chemotherapc treatment.

Preventive Therapy in Patients with Genetic Predisposition

Patients with BRCA1 or BRCA2 mutations have a 60 to 85 percent lifetime risk of breast carcinoma and a 15 to 65 percent lifetime risk of ovarian carcinoma.

The BRCA1 and BRCA2 genes encode proteins that partecipate in the reparative process after a DNA damage.

The genetic predisposition to cancer related to BRCA1 and BRCA2 genes has an autosomal dominant transmission.

Genetic testing for BRCA mutations ic clinically avalaible for patients with familiar breast and ovarian cancers.

Familiar cancers generally occur at a younger age and are often bilateral.

Various clinical studies demonstrated that bilateral oophorectomy reduces the risk of breast and ovarian cancer in patients with BRCA1 or BRCA2 mutations.

Prophylactic bilateral mastectomy (removal of the whole breast glands, including the nipple) represents another choice for the prevention of breast cancer in these patients.

Tamoxifen therapy demonstrated a protective effect among carriers of BRCA2 mutations but not among carriers of BRCA1 mutations (breast carcinomas linked to BRCA1 mutations are usually estrogen-receptor-negative, while tumors associated with BRCA2 mutations are usually estrogen-receptor-positive).