Functional structure of the breast Please review physiology
3 ESENTIAL COMPONENTS Glandular tissue Connective tissue Fatty tissue – Their proportions varies significantly with Age Nutrition status Pregnancy/Post- partum/Lactation
Microscopic structure 1 1.Glandular tissue – Produces milk as final product – lobules completely separated, with radial disposition around the nipple – Galactofore ducts – nipple (small dilated area in the areola, opening in the nipple)
Microscopic structure 2 2 Conective tissue – Creates structure/ support – Included are the suspensory ligaments – Connects the breast to the skin and fascia of the pectoralis major
Microscopic structure 3 3 Fatty tissue – Participates to the structure of the breast – Anterior, posterior and within the lobules – Varies according to diet and can produce major variations in the volume of the breast
Areola Specialized skin adapted for lactation Nipple in the middle Sebaceous glands visible on the surface (Montgomery) Contains smooth muscles which participate in milk evacuation during lactation Highly innervated area
Male breast Rudimentary, areola and nipple Glandular tissue + fatty tissue are – most often- rudimentary or absent. Normal <2cm
Breast development Significant changes in volume and shape according to – Age – Physiologic status In adolescence structure becomes nodular and the volume and structure changes during menstrual cycle.
Aging Volume diminishes Changes in structural proportions – glandular tissue diminishes and is replaced by fat Changes in position due to loss in the elasticity of suspensor structures Loss of axillary hair Sclerosing of ducts
Blood vessels and lymphatics Please review anatomy
Axilary lymph nodes Please review anatomy
Congenital malformations Breast develops from the mammary folds (ectodermic epithelium) on a virtual line (axilla – inguinal ligament) On this line mammary buds develop and regress spontaneously At birth – breast is fully developed and may produce milk under maternal hormonal influence (first days crises)
Congenital anomalies – number and position
Amastia One of the mammary bud lack of development
Polymastia Frequent malformations More gland with incomplete development On the axillary line Mammary ectopy Supranumerary breast may have complete structure and milk secretion May generate diseases like a normal gland
Ately - Politely Congenital absence of the nipple Breast can be normal in structure Lactation is impossible More nipples with or without areola With or without breast tissue
Abnormal positions of the nipple Difficulties during breast feeding Major confusion = retraction of the nipple characteristic of breast cancer
Abnormalities in shape and volume
Atrophy – Dystrophy – Trauma (including surgical) – Congenital – associated with atrophy of pectoralis major – Infections – After radiation Hipertrofia mamara – Uni/bilateral – Excessive growth? – In Endocrine pathology Obesity Surgical cure – Esthetic reason – Psychological reason
Hypotrophy – Reversed form hypertrophy – Uni/bilateral – Mycromasty Surgical correction for esthetic reasons Asymmetry – Major difference between left and right breast – Esthetic and psychological problems – Easy to solve: surgical reduction or breast implant Gynecomasty – Normal/pathologic not mathematical limit – Uni/bilateral – Primary gonadal dysfunction or secundary endocrine imbalance – Adolescent?! ~ normal – Surgical removal
Trauma of the breast Breast contusion – Acute compression on the costal grid – During lactation lesions are more complex: Large galactofore ducts may break Increases risk of infection Steatonecrosis of fat tissue -Residual lesion after contusion -Aseptic necrosis of fat tissue – fat liquefy – pseudocysts form and finally = fibrotic scar Clinical examination: hard nodule, not well delimited – frequent confused with malignancies RESECTION BIOPSY
Traumatic lesions of the breast Wounds – Most frequently stab wounds (precordial area) – In non-lactating breast – no special problem – Lactating breast Wound involving galactofore ducts – high risk of infection Intra-glandular dissemination via ducts Fistula – require the mother to stop lactation
Major forms According to type of tissue – Mastitis: primary infection of glandular structures – Paramastitis (perimastitis) inflammation of connective tissue surrouding glandular structures Types – Acute – Chronic
Mastitis Ethology – Almost exclusively during lactation, usually in the first 2-3 weeks – More frequently after the first child and in women with neglect in the care of the breast (local contamination in all cases) – Bacteria penetrate through small lesions produced in the area of the areola and affect- later on- structures in surrounding tissues
Mastitis – stages of development GALACTOFORITIS – Isolated infection of galactofore ducts (one or more then one lobules) PRESENTATION: Increase in the volume of the breast Pain, both spontaneous and on mombilization. Accentuated during breast feeding Pressure on the nipple: milk + puss through one orifice: differential diagnosis BUDIN sign Non significant general signs of inflammation- fever 38 No axillary lymph nodes enlargements at this stage EVOLUTION: - breast feeding should stop (ATB) + breast emptying. - potentially reversible after antibiotics and anti-inflammatory drugs - may progress to abscess formation
Mastitis - stages BREAST ABSCESS – Suppurative inflammation progresses in connective tissue outside glandular mass CLINICAL PRESENTATION: Accentuated local signs + general signs of inflammation Breast is extremely painful Deformation of the breast: globally enlarged but also not regular shape (small abscesses are more prominent in contour) Budin sign = present Venous stasis – visible veins on the surface of the breast Lymphangitis but no inflammatory lymph node enlargements
Mastitis BREAST ABSCESS – Treatment: ATB + surgical drainage – Recurrent infection : more then one lobule infected in different evolution stages – serial abscess formation – Possible diffusion of infection in the fatty tissues surrounding the breast PARAMASTITIS BREAST FLEGMONOUS INFECTION
Paramastitis Inflammation of the fatty tissue of the breast by inoculation – Direct – Complication of mastitis Forms: – Areolas abscess – Subcutaneous abscess – Retro-mammary abscess
Areolas abscess Acute inflammation of glands on the surface of the areola CLINICAL PRESENTATION: Small tumor in the area of the areola Very thin skin – tendency to evacuate spontaneously Lactation should be discontinued
Subcutaneous abscess Develops subcutaneous Associates lymphangitis Easy to observe collection, superficial, is drained or spontaneous fistulisation
Retro-mammary abscess Inflammation of the fat in the back of the breast Ethiology: mastitis developed in a lobule situated deep in the breast Well developed inflammation signs SPECIFIC: the breast appears as pushed forward due to inflammation behind – Floating sensation – Very painful when mobilized
Forms Hard (wood-like) chronic mastitis (evolution of an acute mastitis) Galactocele Tuberculosis history of Sifilismedicine
Hard (wood-like) mastitis Evolution of an acute form Tendency to develop very slowly New findings – Hard nodules – Orange-skin appearance (adherence to skin) – Permanent retraction of the nipple – Lymph node enlargements Confusion with breast cancer
Galactocele Particular form of chronic mastitis developing during lactation Pseudocyst- cavity of the abscess communicates with one or more large ducts. Contains milk or milky secretion – Pressure on the nipple – secretion containg puss and milk
Galactocele Exploration – ASYMETRIC breast enlargement – ”tumor” with a regular surface – Fluctuence – Painless – Deformable – Thumb print – No inflammatory signs – Secretion contains milk + puss
Fibrocystic disease (Reclus) Most frequent disease of the breast Hormonal influence (most frequent year and unlikely during menopause) Determined factor: estrogen or an imbalance between estrogen and progesteron
Microscopic lesions Typical epithelial lesions are encountered also in the normal breast but have been classified as pathological Typical lesions: – Cysts (macro and microscopical) – Papilomatosis – Adenosis – Fibrosis – Epithelial duct hyperplasis
Clinical presentation Numerous “tumors” uni-/bilateral with no or few symptoms = PAIN is the most important one and points for explorartion of the breast Nipple discharge Symptoms vary during cycle, aggravates premenstrual, nodules change in shape and size and may also disappear.
Differential diagnosis Painbreast Variations in symptomscancer Mammography may help (not beneficial in very young women – breast structure too dense to allow for a good evaluation) Ultrasound + Doppler is probably the best method of evaluation Guided biopsy in cases with doubtful lesions
Treatment Surgical biopsy if any doubt Limited excision under local or general anaestesia Punction for decompression of large cysts (+cytology) FOLLOW UP
Prognostic Alternating periods of rest and exacerbation of symptoms Auto-examination of the breast and seek medical advise if changes develop Risk of cancer is minimally increased only in patients with epithelial dysplasia
Solitary cyst Dystrophic lesion in young women years Large cystic TUMOR with no signs of maligancy. Malignant characteristics would be apparent in such a size. CYST (hard, very hard, well circumscribed) US: liquid content Treatment : punction to evacuate and clinical follow-up
Definitions Breast cancer is a growth of abnormal cells usually within the ducts (which carry the milk to the nipple) or lobules (glands for milk production) of the breast. In more advanced stages of the disease, these out-of-control cells invade nearby tissues or travel throughout the body to other tissues or organs
How does breast cancer develop? 1. Normal ducts 2. Intraductal Hyperplasia 3. Atypical Ductal Hyperplasia 4. Ductal Carcinoma In Situ 5. Invasive Ductal Cancer
Epidemiology Incidence and prevalence Each year the disease is diagnosed in over one million women worldwide and is the cause of death in over 400,000 women, second leading cause of death in women Breast cancer can occur in men, although the incidence is much lower, amounting to around 1% of all breast cancers.
Risk factors Age; Nearly 80% of all newly diagnosed invasive breast cancer cases occur in women aged 50 and older and is less common in premenopausal women. Family history of breast cancer. Paget´s disease accounts for 1% of all breast CA, is associated with an infiltrating, and intraductal carcinoma.
Genetic factors; some cancers have a genetic component and can be inherited. – It is estimated that between 5 and 10% of breast cancer can be attributed to one of two predisposing genes: – BRCA1 – BRCA1 on chromosome 17. – BRCA2 – BRCA2 on chromosome 13. Mutations in these genes are associated with a lifetime
Risk factors Hormone factors: – Early menarche women who started their period before 12 years of age. – Late menopause women who go through menopause after age 55 – Pregnancy history – Pregnancy history: women who have their first child after the age of 30 or who have had fewer pregnancies or no pregnancies. Breast density Breast density: women with less fatty, denser breasts, which are normally older women, have an increased chance of breast cancer. Obesity after menopause Obesity after menopause women who were overweight based on a body mass index (BMI) greater than 25 are 1 to 2 times more likely to die from breast cancer than women with a normal BMI.
Risk factors Ionizing radiation; In 2005, the National Toxicology Program classified X radiation and gamma radiation as known human carcinogens. Compelling scientific evidence points to some of the 100,000 synthetic chemicals in use today as contributing to the development of breast cancer, either by altering hormone function or gene expression.
Risk factors There is broad agreement that exposure over time to estrogens in the body increases the risk of breast cancer. Hormone replacement therapy (HRT) and hormones in oral contraceptives increase this risk – limited increase with oral contraceptives
Risk factors Breast disease – Atpyical Hyperplasia – Intraductal carcinoma in situ – Intralobular carcinoma in situ Diet – Fat – Alcoho l
Types of breast cancer In situ – Intraductal (DCIS) – Intralobular (LCIS) Invasive – Infiltrating ductal carcinoma – Tubular carcinoma – Medullary carcinoma – Mucinous carcinoma
In Situ Breast Cancer In Situ Breast Cancer remains within the ducts or lobules of the breasts. This type of cancer is only detected by mammograms – not by a physical examination. If the cancer is in the duct it is called Ductal Carcinoma in situ. If the cancer is in the lobule of the breast, it is called Lobular Carcinoma in situ. This type of cancer is most common among pre-menopausal women. There is also a slight chance that if a woman has this type of cancer she is at risk that it would occur in the other.
Infiltrating Breast Cancer Breast cancer is considered infiltrating or invasive if the cancer cells have penetrated the membrane that surrounds a duct or lobule. This type of cancer forms a lump that can eventually be felt by a physical examination. Breast cancer cells cross the lining of the milk duct or lobule, and begin to invade adjacent tissues. This type of cancer is called "infiltrating cancer." In this picture, you can see the breast cancer cells invading the milk duct.
More on Infiltrating Breast Cancer Infiltrating cancer of the duct Called “Infiltrating Ductal Carcinoma” It is the most common type of breast cancer. Cancer cells that are invading the fatty tissue around the duct, they stimulate the growth of non- cancerous scar like tissue that surrounds the cancer making it easier to spot. Infiltrating cancer of the lobules Called “Infiltrating Lobular Carcinoma” Occurs when cells stream out in a single file into the surrounding breast tissue. This type of cancer is harder to detect on a mammogram because there is no fibrous growth.
Other Types of Breast Cancer Cystosarcoma Phyllodes Inflammatory Cancer Accounts for less than one percent of all breast cancers and looks as though the breast is infected. Breast Cancer During Pregnancy Paget’s Disease
TNM Criteria T = Primary Tumor Tis = carcinoma in situ T1 = less than 2 cm in diameter T2 = between 2 and 5 cm in diameter T3 = more than 5 cm in diameter T4 = any size, but extends to the skin or chest wall N = Regional Lymph nodes N0 = no regional node involvement N1 = metastasis to movable same side axillary nodes N2 = metastasis to fixed same side axillary nodes N3 = metastasis to same side internal mammary nodes M = Distant Metastasis M0 = no distant metastasis M1 = distant metastasis
Stage 1 Tumor < 2.0 cm in greatest dimension No nodal involvement (N0) No metastases (M0)
Stage II Tumor > 2.0 < 5 cm or Ipsilateral axillary lymph node (N1) No Metastasis (M0)
Stage III Tumor > 5 cm (T3) or ipsilateral axillary lymph nodes fixed to each other or other structures (N2) involvement of ipsilateral internal mammary nodes (N3) Inflammatory carcinoma (T4d)
Stage IV (Metastatic breast cancer) Any T Any N Metastasis (M1)
Screening and Symptoms
Clinical examination Performed by doctor or trained nurse practitioner Annually for women over 40 At least every 3 years for women between 20 and 40 More frequent examination for high risk patients
Mammography X-ray of the breast Has been shown to save lives in patients Data mixed on usefulness for patients Normal mammogram does not rule out possibility of cancer completely
Mammography American Cancer Society recommends: Women (asymptomatic) 40 years of age and older should have a mammogram every year.
Thermograph Thermograph is one of the newest ways to detect breast cancer. Thermograph is a thermal image of the breast tissue. It can also detect cancer before the traditional mammogram can.
Breast Self Examination Opportunity for woman to become familiar with her breasts Monthly exam of the breasts and underarm area May discover any changes early Begin at age 20, continue monthly
When to do BSE Menstruating women- 5 to 7 days after the beginning of their period Menopausal women - same date each month Pregnant women – same date each month Takes about 20 minutes Perform BSE at least once a month Examine all breast tissue
Why don’t more women practice BSE? Fear Embarrassment Youth Lack of knowledge Too busy, forgetfulness
Abnormal signs and symptoms Puckering Dimpling Retraction Nipple discharge Thickening of skin or lump or “knot” Retracted nipple
Abnormal signs and symptoms Change in breast size Pain or tenderness Redness Change in nipple position Scaling around nipples Sore on breast that does not heal
Common Symptoms A change in how the breast or nipple feels – Lump or thickening in or near the breast or in the underarm area – Nipple tenderness A change in how the breast or nipple looks – Change in the size or shape of the breast – Nipple turned inward into the breast – Change in the skin of the breast (“orange” skin, scaly, red, or swollen) Nipple discharge (fluid)
How is Breast Cancer Diagnosed? Screening and/or diagnostic mammography Ultrasound MRI scan Biopsy is necessary to confirm a diagnosis Blood tests are often used to determine if the cancer has spread outside the breast Additional tests may be used to determine stage
Methods of Detection Clinical exam by MD or nurse Mammography Monthly breast self-exam (BSE)
Diagnostic alternatives Screening – abnormal image requiring histology Nodule: discovered during BSE requires clinical examination + immaging + histology Nodule discovered during clinical examination (same) LARGE tumor with clinical characteristics of breast cancer – diagnostic obvious, BUT immaging and histology compulsory
85 Conventionell Mammography Screening A mammogram is an x-ray of the breast, may find tumors that are too small to feel. May find ductal carcinoma in situ, abnormal cells in the lining of a breast duct, which may become invasive cancer in some women. 85
Mammogram Main radiographic examination for breast cancer detection Breast cancer Lesions can be either: – Microcalcifications – Nodules : typically irregular lesion There could be false negative or false positive
May be used along with a mammogram to evaluate breast abnormalities. Performed by a radiologist Allows images from almost any orientation Excellent at imaging cysts Helps for a guided biopsy or FNA Explores a suspicious lymph node. Limits: – lacks the detail of conventional mammography – Unable to image microcalcifications -> not approved as a screening tool for breast cancer diagnosis Ultrasound
88 Ultrasonography- Diagnosis Ultrasonography is useful as a diagnostic adjunct to differentiate cystic from solid tissue in women with nonspecific thichening Doppler effect 88
89 Biopsy- Diagosis If the clinical breast exam, mammogram or ultrasound shows an area of possible concern, a biopsy is usually the next step. A biopsy is the removal of cells or tissues of concern so that they can be viewed under a microscope and further tested by a pathologist.
Needle Aspiration Needle aspiration Cytology Nature of cells: cancerous or not – Advantages: rapid, minimal discomfort, no incision complicating local therapy, immediate results – Limits: no difference between in situ from and invasive cancer, false-negative
Biopsy Biopsy « tru-cut », mamotome Histology – Advantages: rapid, minimal to moderate discomfort, no surgical incision, guided by ultrasound – Limits: false-negative, sampling error with larger lesions DIAGNOSIS
92 To determine if the breast cancer has spread to the lungs.
93 A common place for breast cancer to spread is to the bones. A bone scan is often done to assure there is no detectable metastasis to the bones.
94 positron emission mammography (a PEM scan) The PEM system’s camera and detectors are closer to the area affected with cancer, which produces a very sharp, detailed image of tumors and cancerous tissue. With PEM, cancers can be seen as small as 1.5 – 2mm, about the width of a grain of rice 94
95 MRI combines the use of powerful magnets and radio wave pulses. Used to detect breast cancer in some women at higher risk MRI can also be used before surgery to identify areas of the breast affected by the tumor. 95
Prevention No intervention can completely prevent cancer; there are ways to reduce risk Prophylactic mastectomy (preventive removal of breasts) and prophylactic oophorectomy (preventive removal of ovaries) for women at high risk Chemoprevention (drugs that lower breast cancer risk) with tamoxifen (Nolvadex) or raloxifene (Evista) Risk assessment tools can help those without strong family history discover risk of developing breast cancer
How is Breast Cancer Treated? Treatment depends on stage of cancer More than one treatment may be used Surgery Radiation therapy Chemotherapy Hormone therapy Targeted therapy
Factors Considered in Treatment Decisions The stage and grade (how different cancer cells look from healthy cells) of the tumor The tumor’s hormone receptor status (estrogen receptor [ER], progesterone receptor [PR]) and human epidermal growth factor receptor-2 (HER2) status Genetic description of the tumor The presence of known mutations to breast cancer genes The woman’s menopausal status, age, and general health
Cancer Treatment: Surgery Generally, surgery to remove the tumor followed by radiation therapy is initial treatment For invasive cancer, lymph nodes are removed and evaluated More invasive surgery (such as mastectomy) is not always better; discuss with your doctor Breast reconstruction (plastic surgery) is an option after mastectomy
Principles of Surgery Early Breast Cancer – Targets: breast and nodes – Objectives: to remove the tumor, to get histologic data Curative treatment Advanced and metastatic breast cancer – Target: assessible mass – Objectives: to reduce tumor volume, to remove one isolated metastasis (pulmonary or liver), to treat complications of the disease (spinal compressions…) Palliative treatment
Partial Mastectomy (Lumpectomy) Contraindications – A. Previous history of Radiation Therapy – B. More than one cancer in same breast – C. Large tumor, small breast, cosmetic deformity – D. Nipple involvement
Surgery Terms Excisional Biopsy vs. Lumpectomy Partial Mastectomy vs. Lumpectomy Incisional Biopsy
Mastectomy Difference between Total (simple) Mastectomy Modified Radical Mastectomy
Skin Sparing Mastectomy Skin sparing mastectomy preserves the majority of the breast skin and the inframammary fold The entire nipple and areola are removed
Radical Mastectomy Is Radical Mastectomy still in use? What is it?
Subcutaneous Mastectomy Is Subcutaneous Mastectomy a cancer operation? How does it differ from Total Mastectomy?
Sentinel Node Biopsy Major advance Almost no risk of lymphedema Blue dye Nuclear medicine
Sentinel Lymph Node Biopsy Quickly becoming the gold standard May be as accurate or more accurate than ALN dissection while limiting the complications and costs Involves injection off Technitium-99 sulfur colloid and or 1% isosulfan blue dye
Histological information after surgery of early breast cancer Type of tumor: invasive or in situ, adenocarcinoma or others, ductal or lobular,… Definitive size Histopronosis grade (SBR) Vascular and lymphnode embols Margins +++ Hormonal receptors HER2 status (IHC and/or FISH)
Reconstruction: Tissue expander Encapsulated silicone implant reconstruction corrected with tissue expansion. The capsule is first excised, and the tissue expander is used to create an oversized pocket for the implant.
Reconstruction: Latissimus Dorsi following autogenous latissimus reconstruction w/o implant. Opposite breast reduction mammoplasty required for symmetry.
Reconstruction: TRAM following left free TRAM reconstruction. Skin replacement included all skin between scar & inframammary fold. Nipple reconstruction, opposite mastopexy done at separate procedure.
Breast Reconstruction in the Skin Sparing Mastectomy TRAM flap Latissimus flap Implant/Expander Silicone is preferred and is available on study protocol Tram flap with nipple reconstruction and tatooing
Cancer Treatment: Adjuvant Therapy Treatment given in addition to surgery to reduce the risk of recurrence May include radiation therapy, chemotherapy, targeted therapy, and hormone therapy
Cancer Treatment: Radiation Therapy The use of high-energy x-rays to destroy cancer cells Usually used to treat breast cancer after surgery External-beam: outside the body Internal: uses implants inside the body More precise ways to direct radiation to the tumor and shorter treatment courses are being studied in clinical trials Side effects may include fatigue, swelling, and skin changes
Radiotherapy principles Objectives – Eradicate residual disease thus reduce local recurrence – Increase DFS (disease free survival) and OS (overall survival ) Radiation therapy warranted after breast- conservative surgery Sometimes indicated after mastectomy TREATMENT
Systemic treatment: principles Systemic treatment is recommended under certain circumstances based on prognostic factors and guidelines Treatment objectives: – Reduce the distant metastasis – Increase Time to progression (TTP), – Prolong overall survival In all cases of LABC or MBC Principles: – Chemotherapy – Endocrine therapy – Targeted therapies TREATMENT
Cancer Treatment: Chemotherapy Use of drugs to kill cancer cells May be given before surgery to shrink a large tumor (neoadjuvant chemotherapy) or after surgery to reduce the risk of recurrence (adjuvant chemotherapy) A combination of medications is often used
Cancer Treatment: Hormone Therapy Used to lower risk of recurrence for cancers that test positive for ER and/or PR Tamoxifen is a common hormone therapy effective in many premenopausal and postmenopausal women Aromatase inhibitors (AIs) are also used alone or following tamoxifen use as treatment for postmenopausal women, including anastrozole (Arimidex), letrozole (Femara), and exemestane (Aromasin) Tamoxifen and AIs also used for metastatic cancer; fulvestrant (Faslodex) is another option
Cancer Treatment: Targeted Therapy Treatment that targets genes, proteins, or tumor cell environment that helps cancer grow and survive HER2-targeted therapy: trastuzumab (Herceptin) for HER2-positive breast cancer either with or after adjuvant chemotherapy; lapatinib (Tykerb) plus capecitabine (Xeloda) for advanced or metastatic cancer Anti-angiogenic therapy (blocks blood vessels): bevacizumab (Avastin) for metastatic or recurrent breast cancer Drugs that block bone destruction (bisphosphonates)