• Development – mammary mesenchyme forms the epithelial mammary ridge (milk line) that extends from axilla to groin
• most of mammary ridge regresses by 6^th gestational week except for permanent gland
• supernumerary nipples or accessory breast tissue can develop along line
• Physiologic Changes – responsive to hormones secreted by pituitary, ovary and placenta
• Newborn Infants: transient mammary hyperplasia due to maternal hormones Þ subsides in 3-4 weeks; then no significant changes until puberty
• Puberty and Adolescence: growth and branching of duct system occurs along with proliferation of periductal stroma in response to pituitary and ovarian hormones
• Adult: formed 3-4 years following initial hormone surge; undergoes cyclic changes in response to the hormonal changes of the menstrual cycle
• Pregnancy: placental secretion of human placental lactogen and HCG along with estrogen and progesterone promotes growth of lobules and initiate secretory activity
• Normal Gross Anatomy
• Female – each breast contains 12-20 branching ducts that start at the nipple and end in the lobules or acini
• acini are the secretory units of the duct
• ducts and acini are embedded in fibrous and adipose tissue; fibrous septae (Cooper’s Ligaments) extend from the skin to the underlying pectoralis fascia
• terminal duct is the site of most benign and malignant breast disorders
• Male – contain ductules but lack lobules
• Microscopic Anatomy
• duct system is lined by two layers of cells: inner epithelial and outer myoepithelial cells (smooth muscle)
• acini/lobules are embedded in loose intralobular stroma (hormonally responsive); ducts are separated by dense collagenized fibrous tissue and adipose tissue

• Congenital Anomalies: supernumerary/accessory nipple (most common), ectopic breast tissue (2-3%), unilateral hyopoplasia, amastia (absence of breast)
• Mastitis and Abscess: painful, localized areas of acute inflammation, usually in lactating women, sometimes older
• usually bacterial cause; may progress to abscess
• chronic mastitis (plasma cell mastitis, lymphocytic mastitis and granulomatous mastitis) rarely involve breast
• Fibrocytic Changes – most common disease of the breast
• variety of benign mammary alteration that are considered exaggerated physiologic phenomena
• fibrosis replaces adipose tissue and cysts and can cause cyst dilation
• associated with increased risk of breast cancer only if hyperplasia is severe and atypical
• Age Group: premenopausal women between 20-50 are most frequently affected; usually bilateral
• Clinical Presentation: breast swelling and/or tenderness – generally small, hard, tender nodules – pain and tenderness can be debilitating; single or multiple large lumps palpable; tenderness cycles with menstration
• mammography indicates diffuse density secondary to extensive CT proliferation and fibrosis – microcalcification
• usually involute during menopause due to lack of estrogen
• Gross Appearance – 1-2 mm blue domed or clear cysts of firm indistinct fibrous tissue
• Microscopic Appearance – cystic dilation of ducts, aprocrine metaplasia, sclerosing adenosis, fibrosis, periductal inflammation, microcalcifications and ductal/lobular epithelial hyperplasia
• sclerosing adenosis is the most characteristic histologic finding of fibrocytic changes
• Subtypes of Fibrocytic Changes:
• Fibroadenoma – most common benign breast lesion – no risk of malignancy
• Age: peak incidence in 3^rd decade
• Clinical Presentation: single discrete non-tender movable and palpable mass 2-3 cm in size
• Histologically: proliferation of ductal/epithelial and stromal/mesenchymal elements
• Treatment: simple excision
• Fat Necrosis – usually result of traumic injury to fat cells causing inflammation and granulomatous tissue
• mammogram indicates irregular density with microcalcifications
• Histology: foreign-body type reaction with macrophages and multinucleated giant cells
• Intraductal Papilloma – neoplastic proliferation of duct epithelium in dilated duct producing a papillary mass
• multiple small papillomas are often seen; large solitary papillomas common in older women
• Clinical Presentation: bloody or serous nipple discharge
• Histology: very similar to low-grade papillary carcinoma

Malignant Diseases – breast cancer is the most common and 2^nd most lethal cancer in women (lung cancer is 1^st)

• Classifications:
• (1) Carcinoma in situ (CIS)
• (a) Ductal Carcinoma in situ (DICS, a.k.a. intraductal carcinoma) – most common type of breast cancer discovered on routine mammography
• Cancer Risk: 14% develop infiltrating carcinoma after 17 years, 6% develop reoccurrance
• Mammography: density and/or microcalcifications
• Histologically: malignant cells limited to ducts with no stromal invasion
• solid, cribiform, papillary or micropapillary, comedo (central necrosis)
• nuclear grade (degree of nuclear atypia) ranges from low intermediate to high grade
• comedo form is associated with a higher malignancy risk
• Treatment: surgical incision with clear margins; axillary lymph node is not involved (but malignant cells are found there 1-2% of the time, indicating carcinoma is actually invasive)
• (b) Lobular carcinoma in situ (LCIS) – arises in terminal ducts/lobules; usu. incidental finding in breast biopsies; more often bilateral than DCIS
• Cancer Risk: less than DCIS
• (2) Infiltrating Carcinoma
• (a) Infiltrating Ductal Carcinoma – most common type of invasive BC (50-75%); usually affects older women
• Clinical Presentation: palpable mass or abnormality on mammogram
• Histology: solid nests and tubules/glands formed by the malignant cells infiltrate the fibroadipose stroma of breast
• (b) Infiltrating Lobular, Tubular, Medullary, Colloidal and Papillary Carcinomas – rare, not specific to breast
• Histology: classified as low, intermediate, or high grade
• Staging: size of primary lesion, extent of spread to lymph nodes, presence/absence of blood-borne metastases
• stage is the most important prognostic indicator
• Methods of Evaluation
• Self-examination – monthly, preferably after onset of menses when hormonal stimulation is minimal
• Mammography – can detect cancer 1-2 years before clinically palpable; can detect lesions < 1 cm
• Ultrasound – used mostly to differentiate cystic from solid lesions
• Fine Needle Aspiration (FNA) Biopsy – required in case of solid masses, bloody fluids, or recurrent cysts
• clear or yellow fluid is not concerning
• Excision/Needle Localization Biopsy
• Epidemiology of Breast Cancer – incidence Ý with age
• Genetics of Breast Cancer: 5-10% of cases are thought to be associated with specific inherited mutations of BRCA-1 on ch.17
• 50% of women with BRCA-1 mutation will develop BC by age 65
• BRCA-2 is on chromosome 13 and is associated with 10% of inherited BC
• Risk Factors
• Family history: Ý risk if family members had premenopausal and/or bilateral BC
• Menstrual history: Ý risk with menarche < 12 or menopause > 55
• Parity: Ý risk with no or fewer children
• Benign Breast Diseases: Ý risk with CIS > Proliferative with atypical hyperplasia > Proliferative
• Other Factors: exogenous estrogen, obesity, Ý fat diet, alcohol and tobacco associated with Ý risk
• Treatments
• surgery – Lumpectomy/Quadretectomy/Segmental Resection, Mastectomy, Axillary Lymph Node Dissection
• radiation therapy; combined lumpectomy and radiation therapy now has same prognosis as total mastectomy
• systemic chemotherapy

Male Lesions – gynecomastia, carcinoma