malignant breast disorders · accounts for 4%. grossly, the cancer is soft and hemorrhagic. a rapid...
TRANSCRIPT
Malignant Breast disorders
RISK FACTORS FOR BREAST CANCER
• Family Hx.: first- and second-degree relatives with breast cancer and their age at diagnosis.
RISK FACTORS FOR BREAST CANCER (cont.)
Hormonal Risk Factors • ↑ exposure to estrogen → ↑ risk for breast cancer: -factors that increase the number of menstrual cycles, such as early menarche, nulliparity, and late menopause, are associated with increased risk. -obesity is associated increased breast cancer risk. Because the major source of estrogen in postmenopausal women is the conversion of androstenedione to estrone by adipose tissue, obesity is associated with a long-term increase in estrogen exposure. -so older age at first live birth is associated with an increased risk of breast cancer
• whereas ↓ exposure → thought to be protective. -Moderate levels of exercise and a longer lactation period, factors that decrease the total number of menstrual cycles, are protective. -The terminal differentiation of breast epithelium associated with a full-term pregnancy is also protective, so older age at first live birth is associated with an increased risk of breast cancer.
RISK FACTORS FOR BREAST CANCER (cont.)
Nonhormonal Risk Factors
• radiation exposure.
Survivors of the atomic bomb blasts in Japan during World War II have a very high incidence of breast cancer,
radiation exposure during adolescence, a period of active
• breast development, magnifies the deleterious effect.
• alcohol consumption increases the risk of breast cancer. Alcohol consumption is known to increase serum levels of estradiol.
• long-term consumption of foods with a high fat contributes to an increased risk of breast cancer by increasing serum estrogen levels.
Risk Management e.g.
• when to use postmenopausal hormone replacement therapy.
• at what age to begin mammography screening or incorporate magnetic resonance imaging (MRI) screening.
• When to use tamoxifen to prevent breast cancer.
• when to perform prophylactic mastectomy to prevent breast cancer.
• Breast Cancer Screening.
• When Risk-reducing salpingo-oophorectomy
• When Chemoprevention.
EPIDEMIOLOGY AND NATURAL HISTORY OF BREAST CANCER
Epidemiology
• Breast cancer is the most common site-specific cancer in women and is the leading cause of death from cancer for women aged 20 to 59 years.
• The increase in breast cancer incidence occurred primarily in women ≥55 years.
• There is a 10-fold variation in breast cancer incidence among different countries worldwide.
Natural History
• Bloom and colleagues described the natural history of breast cancer based on the records of 250 women with untreated breast cancers who were cared for on charity wards in the Middlesex Hospital, London, between 1805 and 1933.
Primary Breast Cancer. • More than 80% of breast cancers show
productive fibrosis that involves the epithelial and stromal tissues.
• entraps and shortens Cooper’s suspensory ligaments to produce a characteristic skin retraction.
• Localized edema (peaud’orange) develops when drainage of lymph fluid from the skin is disrupted.
• cancer cells invade the skin, and eventually ulceration occurs.
• As new areas of skin are invaded, small satellite nodules appear near the primary ulceration.
Axillary Lymph Node Metastases
• As primary breast cancer increases, some cancer cells are shed into cellular spaces and transported via the lymphatics the to the regional lymph nodes, especially axillary LNs.
• LNs that contain mets cancer are at first ill-defined and soft but become firm or hard with continued growth of the mets.
• Eventually LNs adhere to each other and form a conglomerate mass.
• Cancer cells may grow through LN capsule and fix to structures in the axilla, including the chest wall.
Distant Metastases • At approximately the twentieth cell doubling, breast cancers
acquire their own blood supply (neovascularization). • Thereafter, cancer cells may be shed directly into the systemic
venous blood to seed the pulmonary circulation via the axillary and intercostal veins or the vertebral column.
• These cells are scavenged by natural killer lymphocytes and macrophages.
• Successful mets foci from breast cancer predictably occurs after the primary cancer exceeds 0.5 cm in diameter, which corresponds to the twenty-seventh cell doubling.
• For 10 years after initial treatment, distant metastases are the most common cause of death in breast cancer patients. Metastases may become evident as late as 20 to 30 years after treatment
• Common sites of involvement, in order of frequency, are bone, lung, pleura, soft tissues, and liver. Brain metastases are less
HISTOPATHOLOGY OF BREAST CANCER
Carcinoma In Situ
• Cancer cells are in situ or invasive depending on whether or not they invade through the basement membrane. ductal and alveolar.
• Lobular Carcinoma In Situ. LCIS: originates from the terminal duct lobular units and develops only in the female breast.
• Ductal Carcinoma In Situ (DCIS): Although DCIS is predominantly seen in the female breast, it accounts for 5% of male breast cancers. Histologically, DCIS is characterized by a proliferation of the epithelium that lines the minor ducts, resulting in papillary growths within the duct lumina.
HISTOPATHOLOGY OF BREAST CANCER
Invasive Breast Carcinoma
• ldescribed as lobular or ductal in origin.
• invasive ductal carcinoma of no special type (NST).
• Foote and Stewart originally proposed the following classification for invasive breast cancer125:
1. Paget’s disease of the nipple
2. Invasive ductal carcinoma—Adenocarcinoma with productive
fibrosis (scirrhous, simplex, NST), 80%
3. Medullary carcinoma, 4%
4. Mucinous (colloid) carcinoma, 2%
5. Papillary carcinoma, 2%
6. Tubular carcinoma, 2%
7. Invasive lobular carcinoma, 10%
8. Rare cancers (adenoid cystic, squamous cell, apocrine)
Paget’s disease of the nipple: frequently presents as a chronic, eczematous eruption of the nipple, which may be subtle but may progress to an ulcerated, weeping lesion. Paget’s disease usually is associated with extensive DCIS and may be associated with an invasive cancer.
Invasive ductal carcinoma of the breast with productive fibrosis (scirrhous, simplex, NST): accounts accounts for 80% of breast cancers.
Medullary carcinoma is a special-type breast cancer; it
Accounts for 4%. Grossly, the cancer is soft and hemorrhagic. A rapid increase in size may occur secondary to necrosis and hemorrhage. Bilaterality is reported in 20% of cases.
Mucinous carcinoma (colloid carcinoma),: another specialtype breast cancer, accounts for 2% of all invasive breast cancers. defined by extracellular pools of mucin.
Papillary carcinoma: accounts for 2% of all invasive breast cancers.
defined by papillae with fibrovascular stalks and multilayered epithelium. showed a low frequency of axillary lymph node metastases
• Tubular carcinoma: accounts for 2%. Under low-power
magnification, a haphazard array of small, randomly arranged tubular elements is seen.
• Invasive lobular carcinoma: accounts for 10%. It is
frequently multifocal, multicentric, and bilateral.
DIAGNOSIS OF BREAST CANCER
• Discussed in benign breast disorders.
• Hx
• Physical Examination
• Investigations.
Breast Cancer Staging • The clinical stage of breast cancer is determined primarily
through physical examination of the skin, breast tissue, and regional lymph nodes (axillary, supraclavicular, and internal mammary).
• Ultrasound (US) is more sensitive than physical examination alone in determining axillary lymph node involvement.
• Fine-needle aspiration (FNA) or core biopsy of sonographically indeterminate or suspicious lymph nodes can provide a more definitive diagnosis than US alone.
• Sentinel node dissection is the preferred method for staging of the regional lymph nodes in women with clinically node-negative invasive breast cancer. Axillary dissection may be avoided in women with 1 to 2 positive sentinel nodes who are treated with breast conserving surgery.
• whole breast radiation and systemic therapy.A frequently used staging system is the TNM (tumor, nodes, and metastasis) system.
SURGICAL APPROACHES TO CANCER THERAPY
• Multidisciplinary Approach to Cancer
• Although surgery is an effective therapy for most solid tumors, patients who die from cancer usually die of metastatic disease.
• In most instances, a multidisciplinary approach beginning at the patient’s initial presentation is likely to yield the
• best result.
• Surgical Management of Primary Tumors
• The goal of surgical therapy for cancer is to achieve oncologic cure.
• A curative operation presupposes that the tumor is confined to the organ of origin or to the organ and the regional lymph node basin.
• Patients in whom the primary tumor is not resectable with negative surgical margins are considered to have inoperable disease.
• The operability of primary tumors is best determined before surgery with appropriate imaging studies.
• Disease involving multiple distant metastases is deemed inoperable because it is usually not curable with surgery of th primary tumor.
• On occasion, primary tumors are resected in these patients
for palliative reasons,
• It is important to determine optimum surgical margins for each cancer type so that adjuvant radiation and systemic therapy can be offered to patients
• There are also ongoing studies on approaches to assess margins intraoperatively, to allow immediate intraoperative reexcisions as needed, and maximizing local control.
Surgical Management of the Regional Lymph Node Basin
• Most neoplasms have the ability to metastasize via the lymphatics.
• most oncologic operations have been designed to remove the primary tumor and draining lymphatics en bloc.
• Surgical management of the clinically negative regional lymph node has evolved with the introduction of lymphatic mapping technology.
• Lymphatic mapping • and sentinel lymph node biopsy specimen were first
reported • in 1977 by Cabanas for penile cancer. Now, sentinel node
biopsy specimen is the standard of care for the management of melanoma and breast cancer.
• The first node to receive drainage from the tumor site is termed the sentinel node. It is the node most likely to contain metastases, if metastases to that regional lymph node are present.
Surgical Management of Distant Metastases
• The treatment of a patient with distant metastases depends on the number and sites of metastases, the cancer type, the rate of tumor growth, the previous treatments delivered and the responses to these treatments, and the patient’s age, physical condition, and desires.
CHEMOTHERAPY • Clinical Use of Chemotherapy
• In patients with documented distant metastatic disease, chemotherapy is usually the primary modality of therapy.
• Adjuvant therapy can be administered after surgery (postoperative chemotherapy), or before surgery (preoperative chemotherapy neoadjuvant chemotherapy, or inductio therapy).
• Chemotherapy destroys cells by first-order kinetics, which means that with the administration of a drug a constan percentage of cells is killed, not a constant number of cells.
• Cell- cycle phase-nonspecific agents (e.g., alkylating agents) have a linear dose-response curve, such that the fraction of cells killed increases with the dose of the drug.
• In contrast, the cell-cycle phase-specific drugs have a plateau with respect to cell killing ability, and cell kill will not increase with further increases in drug dose.
• Anticancer Agents:
• Alkylating Agents
• Antitumor Antibiotics.
• Antimetabolites.
• Plant Alkaloids.
• Combination Chemotherapy
RADIATION THERAPY
• Radiation therapy may be used as the primary modality for palliation in certain patients with metastatic disease, primarily patients with bony metastases.
• Adjuvant radiation therapy can be given before surgery, after surgery, or, in selected cases, during surgery.
HORMONAL THERAPY • The first attempts at hormonal therapy were
through surgical ablation of the organ producing the hormones involved, such as oophorectomy for breast cancer.
• Currently, hormonal anticancer agents include androgens, antiandrogens, antiestrogens, estrogens, glucocorticoids, gonadotropin inhibitors, progestins. such as with the estrogen antagonist tamoxifen.
• In breast cancer, estrogen and progesterone receptor status is used to predict the success of hormonal therapy. Androgen receptor is also being pursued as a therapeutic target for breast cancer treatment.
• TARGETED THERAPY: Over the past decade, increased understanding of cancer biologyhas fostered the emerging field of molecular therapeutics.The basic principle of molecular therapeutics is to exploit themolecular differences between normal cells and cancer cells todevelop targeted therapies.
• IMMUNOTHERAPY: The aim of immunotherapy is to induce or potentiate inherent antitumor immunity that can destroy cancer cells.
• GENE THERAPY: Gene therapy is being pursued as
a possible approach to modifying the genetic program of cancer cells as well as treating metabolic diseases.
Breast Cancer Prognosis • Survival rates for women diagnosed with breast cancer in the
United States can be obtained from the SEER Program of the National Cancer Institute.
• The overall 5-year relative survival for breast cancer patients from the time period of 2003–2009 from 18 SEER geographic areas was 89.2%.
• The 5-year relative survival by race was reported to be 90.4% for white women and 78.7% for black women.
• The 5-year survival rate for patients with localized disease (61% of patients) is 98.6%; for patients with regional disease (32% of patients), 84.4%; and for patients with distant metastatic disease (5% of patients), 24.3%.
Local-Regional Recurrence • Women with local-regional recurrence of breast cancer may
be separated into two groups: those who have had mastectomy and those who have had lumpectomy.
• Women treated previously with mastectomy undergo surgical resection of the local-regional recurrence and appropriat reconstruction. Chemotherapy and antiestrogen therapy are considered, and adjuvant radiation therapy is given if the chest wall has not previously received radiation therapy or if the radiation oncologist feels that there is scope for further radiation therapy, particularly if this is palliative.
• Women treated previously with a breast conservation procedure undergo a mastectomy and appropriate reconstruction. Chemotherapy and antiestrogen therapy are considered.
Local-Regional Recurrence: • Women with local-regional recurrence of breast cancer
may be separated into two groups: those who have had mastectomy and those who have had lumpectomy.
• Women treated previously with mastectomy undergo surgical resection of the local-regional recurrence and appropriate reconstruction. Chemotherapy and antiestrogen therapy are considered, and adjuvant radiation therapy is given if the chest wall has not previously received radiation therapy or if the radiation oncologist there is scope for further radiation therapy, particularly if this is palliative.
• Women treated previously with a breast conservation procedure undergo a mastectomy and appropriate reconstruction. Chemotherapy and antiestrogen therapy are considered.
SURGICAL TECHNIQUES IN BREAST CANCER THERAPY
Excisional Biopsy with Needle Localization
• Excisional biopsy implies complete removal of a breast lesion with a margin of normal-appearing breast tissue.
• important to consider the options for local therapy (lumpectomy vs. mastectomy with or without reconstruction) and the need for nodal assessment with SLN dissection.
• After excision of a suspicious breast lesion, the specimen should be x-rayed to confirm the lesion has been excised with appropriate margins.
Breast Conservation • Breast conservation involves resection of the primary
breast cancer with a margin of normal-appearing breast tissue, adjuvant radiation therapy, and assessment of regional lymph node status.
• Resection of the primary breast cancer is alternatively called segmental mastectomy, lumpectomy, partial mastectomy, wide local excision, and tylectomy.
Mastectomy and Axillary Dissection • A skin-sparing mastectomy removes all breast tissue, the
nipple-areola complex, and scars from any prior biopsy procedures
• A total (simple) mastectomy without skin sparing removes all breast tissue, the nipple-areola complex, and skin.
• An extended simple mastectomy removes all breast tissue, the nipple-areola complex, skin, and the level I axillary lymph nodes.
• A modified radical (‘Patey’) mastectomy removes all breast tissue, the nipple-areola complex, skin, and the levels I, II and III axillary lymph nodes: the pectoralis minor which was divided and removed by Patey may be simply divided, giving improved access to level III nodes, and then left in-situ or occasionally the axillary clearance can be performed without dividing pectoralis minor.
• The Halsted radical mastectomy • Nipple-areolar sparing mastectomy
