Outline for Breast Cancer: 
Embryology:
Lactiferous ducts – derived from the epithelial layers. 
Breast stroma – derived from the mesoderm. Includes smooth muscle, cells, capillary endothelial cells and adipocytes. 

Breast Development: 
During puberty an estrogen surge leads to the development of breast buds. This surge triggers pituitary growth hormone to stimulate mammary gland production of insulin-like growth factor-1 (IGF-1). Which in turn leads breast formation. 

Anatomy: 
Breast borders: 

• sternum medially, clavicle superiorly, IMF inferiorly, and the anterior border of the latissimus muscle laterally

Nipple Sensation and Perfusion: 

• Blood Supply to the NAC: perforators of the IMA although also does receive perfusion from the lateral thoracic artery 

• The NAC sensation is mainly derived from the lateral 4^th intercostal nerve, However, after mastectomy the anterior fourth intercostal nerve is most likely to provide nipple sensation as it courses more superficially. 

Benign breast disease:
There are a number of benign breast diseases – however the ones that we get asked most frequently about are: 

• Common fibroadenoma: most common breast tumor in adolescent females (14-16). Treatment is excisional biopsy or observation. 

• Phyllodes Tumor: stomal tumor and is the most common non-epithelial tumor or the breast. This is a locally aggressive disease but rarely malignant. Treatment is wide surgical margins of at least 1cm are recommended to decrease risk of recurrence.

• Papilloma: polyp of epithelium lined breast ducts
• Nipple papillomas present typically with bloody nipple discharge. Treatment is excision
• If this is fully excised in breast reconstruction or reduction no further management is necessary (maybe a mammogram if this is offered in test question)

 Breast Cancer: 
Breast Cancer Screening:

• ACS recommends average risk patients receive screening mammogram at 40-44 years (optional); annual screening from 45-54, and biennial screening for >55 years of age who are in good health and have a life expectancy of at least 10 years.
• In a newly found mass <35 years evaluate with ultrasound; >35 diagnostic mammogram with ultrasound.
• Screening mammography consists of two views and is appropriate for asymptomatic patients 
• Diagnostic mammography incorporates additional views for abnormalities listed above.

Breast Cancer: 

• Atypia of the Breast: 
• Considered atypical breast pathology that are markers of increased risk of developing breast cancer but are not precursors to breast cancer such as DCIS 
• Includes ADH, LCIS, ALH and radial scar. There are all markers of increased risk 
• Atypical hyperplasia: 4-5 fold increased risk for developing breast cancer.  
• LCIS – this is a marker of increased risk in the bilateral breasts. Further, most patients that have LCIS and go on to develop cancer, end up with a ductal cancer NOT a lobular cancer 
• Treatment: 
• Surgical:  excisional biopsy to look for synchronous breast cancer in the same area. DO NOT need negative margins (meaning it is okay if you still find LCIS on the border of the excisional biopsy specimen) . 
• Medical: 
• If there is no cancer in the excisional biopsy then place the patient on tamoxifen or AI as a risk reducing measure 
• If there is cancer in the excisional biopsy treat like an invasive cancer (see below)

• Staging of breast cancer: TNM staging 
• T: Tis (in situ); T1 <2cm, T2 2-5cm, T3 >5cm, T4 extension into chest wall or skin
• N0 no lymph nodes, N1 1-3 nodes, N2 4-9 nodes, N3 >10 nodes
• M0 no metastasis; M1 metastasis

• DCIS:
• Definition: Stage 0 breast cancer defined as the presence of malignant-appearing cells confined to the lumen of the ductal system or do not invade the basement membrane of the ductal system 
• This is considered a pre-malignant lesion to invasive cancer and therefore the purpose of treatment is to prevent progression to invasive cancer with the sequelae of metastatic disease.
• If left untreated, 50-60% will progress to an ipsilateral invasive cancer
• Treatment: 
• Surgical excision 
• Lumpectomy + Radiation.  
• Mastectomy 
• The decision to undergo mastectomy is based on the size of the area involved with DCIS and the size of the breast. 
• Margins for DCIS need to be 2mm to be considered a negative margin 
• There is no need for axillary staging with lumpectomy however, with mastectomy you lose the ability to map sentinel nodes therefore it is recommended that the surgeon perform SLNBx at the time of mastectomy in case of upstaging on final pathology. 

• Ductal adenocarcinoma is the most common form of breast cancer and arises from glandular tissue.
• Basic Facts
• 12% of women develop breast cancer
• Family history increases that risk to 15%
• Risk increases up to 45% if there is a history of bilateral and premenopausal familial cancer.

• Treatment: Multidisciplinary approach including chemotherapy, radiation therapy, surgery, and endocrine therapy. 

• Surgery 

• Breast conserving therapy followed by radiation
• Contraindications to breast conserving therapy include: 
• Multicentric disease with two or more tumors in separate quadrants of the breast such that they cannot be encompassed by a single excision
• History of prior radiation in the same breast or chest wall
• Pregnancy 
• Persistently positive margins despite re-excision
• Relative contraindications to breast conserving therapy include: 
• Collagen vascular disease such as lupus and scleroderma
• Hereditary breast disease
• Small sized breasts relative to the size of the tumor 
• Margin status: no tumor on the inked margin 
• Mastectomy: 
• Nipple Sparing Mastectomy: Exclusion Criteria 
• tumor size >5cm
• location <2cm from the nipple 
• Skin involvement including Paget’s disease
• Axillary disease

CPM data:

• Women with BRCA benefit from risk reduction
• No proven oncologic benefit to contralateral prophylactic mastectomy (CPM) in those with average risk. It has not been proven to improve cure rate, reduce recurrence, and INCREASES number of operations
• BRCA1/2 are associated with breast/ovarian cancers; can also be associated with pancreatic and prostate cancer
• BRCA1 – 65% breast cancer by age 70, 35-70% ovarian cancer by age 70
• BRCA2 – 55% by age 70, 10-30% ovarian cancer by age 70
• Radiation Therapy: 
• National Comprehensive Cancer Network (NCCN) guidelines for radiation therapy: 
• Radiation following lumpectomy: following breast conserving therapy
• Radiation following mastectomy:
• is larger than 5 cm (about 2 inches)
• has spread to four or more lymph nodes 
• has positive or close surgical margins (<5mm) 
• has spread to the skin
• Radiation therapy sequela: 
• acute includes erythema, edema, desquamation, hyperpigmentation, and ulceration
• Chronic injury includes atrophy, dryness, telangiectasia, dyspigmentation, dyschromia, and fibrosis
• Medications:
• Aromatase inhibitors impair conversion of androgens to estrogen
• Tamoxifen: selective estrogen receptor modulator
• Associated with thromboembolic events, increased rates of flap loss and decreased rates of flap salvage
• Should be held 28 days pre-operatively in patients undergoing microsurgical breast reconstruction