Breast Flashcards
Breast carcinoma summary
Breast cancer is the most common malignancy in women. The lifetime risk of developing breast cancer for women in the USA is approx. 12%. The most important risk factors include increased estrogen exposure, advanced age, and genetic predisposition (BRCA1/BRCA2 mutations). Most breast cancers are adenocarcinomas. Histopathologic classification differentiates between ductal and lobular carcinomas. The two most common types of breast cancer are invasive ductal carcinoma, which accounts for 70–80% of all cases, and the less aggressive invasive lobular carcinoma. Both types typically develop from noninvasive carcinomas, i.e., ductal carcinoma in situ (DCIS), and lobular carcinoma in situ (LCIS), respectively.
The majority of breast cancers are detected during routine mammography screening, which is recommended every two years in women aged 50–74 years. Alternatively, women may present with a self-palpated breast lump. Mammographic abnormalities and breast masses require further radiographic evaluation, and, if there are signs of malignancy or the results are inconclusive, histopathologic analysis (biopsy). The axillary lymph node status is determined through clinical examination and biopsy of a suspicious lymph node or sentinel lymph node.
The treatment approach primarily depends on the histopathologic classification and the disease stage and involves a combination of surgical management, radiation therapy, and systemic therapy. Surgical management is either breast-conserving therapy (BCT) or mastectomy. Systemic therapy has significantly improved in recent years with the development of hormone therapy (tamoxifen) and targeted therapy (trastuzumab). The most important prognostic factors are lymph node status, tumor size, patient’s age, and tumor receptor status (hormone receptors and HER2).
Women with a high risk of developing breast cancer (i.e., positive BRCA mutation status) should be offered genetic counseling and risk-reducing prophylactic surgery.
Breast carcinoma Dr Deac Pimp
Epidemiology:
Incidence: most common malignant disease in women (∼ 30% of all malignancies in women)
Peak incidence: postmenopausal
Mortality: second leading cause of cancer death in women in the US
One in 8 women in the USA (∼12 %) will develop invasive breast cancer during their lifetime!
Aetiology:
Predisposing factors
Breast cancer in the contralateral breast ; history of ovarian, endometrial, or colorectal cancer
Increased estrogen exposure
High number of total menstrual cycles
Early menarche, late menopause
Nulliparity
First full-term pregnancy after age 35 years
Exogenous estrogen intake: hormone replacement therapy after menopause
BRCA1 or BRCA2 gene mutations
Autosomal-dominant inherited gene mutation
Associated with an increased risk for breast cancer (∼ 70%) and ovarian cancer
BRCA-positive women develop breast cancer approx. 15–20 years earlier than women without the mutation.
BRCA mutations are found in 5–10% of all women with breast cancer.
Positive family history (e.g. affected first-degree relatives)
Positive history of breast conditions (e.g., fibrocystic change, fibroadenoma) with cellular atypia
Previous radiation treatment in childhood
Lifestyle factors: low-fiber and high-fat diet, smoking, alcohol consumption, obesity in postmenopausal women
Associated genetic diseases
Li-Fraumeni syndrome (Sarcoma, Breast, Leukemia and Adrenal Gland cancer syndrome (SBLA))
Autosomal dominant inherited mutation of the p53 tumor suppressor gene (TP53)
Loss of heterozygosity: one abnormal copy of the TP53 gene is inherited → second allele is somatically mutated or deleted → unregulated cell proliferation and cancer
Multiple malignancies at an early age: breast cancer, osteosarcoma, leukemia, lymphoma, brain tumor, adrenocortical carcinoma
Peutz-Jeghers syndrome
Overview
Most breast cancers are adenocarcinomas, arising from ductal tissue (80%) or lobular tissue (20%).
Noninvasive (in situ) carcinomas
Ductal carcinoma in situ (DCIS)
∼ 25% of all newly diagnosed breast cancers
Localization: unifocal
Frequently has a pattern of grouped microcalcifications
Higher risk of subsequent invasive carcinoma (ipsilateral)
Lobular carcinoma in situ (LCIS)
1–5% of all newly diagnosed breast cancers
Localization: multifocal
Microcalcifications are rare
Lower risk of subsequent invasive carcinoma (equal predisposition in both breasts)
The noninvasive carcinomas are characterized by the absence of stromal invasion!
Invasive carcinomas
Invasive ductal carcinoma (most common)
70–80% of all invasive breast carcinomas
Unilateral localization
Mostly unifocal tumors
More aggressive, early metastases
Invasive lobular carcinoma
10–15% of all invasive breast carcinomas
Unilateral or bilateral
Frequently multifocal
Less aggressive than ductal carcinoma
Slower metastasis than ductal carcinoma
Less common subtypes: mucinous (< 5% ), medullary (5%), tubular (1–2% )
Inflammatory breast cancer
Clinical features
Patients with breast cancer develop clinical symptoms rather late at advanced tumor stages. Typical signs may include:
Changes in breast size and/or shape; asymmetric breasts
Palpable mass: typically a single, nontender, firm mass with poorly defined margins, most commonly in the upper outer quadrant
Skin changes
Retractions or dimpling (due to tightening of the Cooper ligaments)
Peau d’orange: skin resembling an orange peel (due to obstruction of the lymphatic channels)
Redness, edema, and pitting of the hair follicles
Nipple changes: inversion, blood-tinged discharge
Axillary lymphadenopathy: firm, enlarged lymph nodes (> 1 cm in size), that are fixed to the skin or surrounding tissue
In advanced stages: ulcerations
Subtypes and variants
Paget disease of the breast
Definition: a ductal carcinoma (usually adenocarcinoma- either in situ or invasive) that infiltrates the nipple and areola
Clinical features
Erythematous, scaly, or vesicular rash affecting the nipple and areola
Pruritus, burning sensation, nipple retraction
The lesion eventually ulcerates → blood-tinged nipple discharge
Diagnostics
Nipple scrape cytology: large, round cells with prominent nuclei
Punch or wedge biopsy
Differential diagnosis: mamillary eczema
Treatment: surgical treatment, if possible using a breast-conserving procedure (see “Treatment” below).
Paget disease of the breast
Inflammatory breast cancer
Definition: a rare form of advanced, invasive carcinoma, characterized by dermal lymphatic invasion of tumor cells. Most commonly a ductal carcinoma.
Clinical features
Erythematous and edematous (peau d’orange) skin plaques over a rapidly growing breast mass
Tenderness, burning sensation, blood-tinged nipple discharge
Axillary lymphadenopathy
25% of patients have metastatic disease at the time of presentation
Differential diagnosis: mastitis, breast abscess, Paget disease of the breast
Treatment: chemotherapy + radiotherapy + radical mastectomy
Poor prognosis: 5-year survival with treatment: ∼ 50% (without treatment: < 5%).
Diagnostics:
Approach to suspected breast cancer
Most patients present with abnormalities detected during routine mammography screening. Alternatively, young women in particular (who are not routinely screened) present with a self-palpated breast mass. The diagnostic approach involves clinical assessment, radiographic imaging, and biopsy.
Clinical assessment
Certain constellations of patient characteristics should raise suspicion for malignancy in a breast lump, warranting further assessment.
Radiographic imaging
Mammography
Although mammography does not confirm the diagnosis, it is primarily useful for early detection of breast abnormalities!
Breast ultrasound
Distinguish between solid lesions and benign cysts
Evaluate axillary, supraclavicular, and infraclavicular lymph nodes
Provide guidance in interventional procedures (fine needle aspiration, core needle biopsy)
Biopsy
Core needle biopsy (CNB) : confirms the diagnosis (preferred test) and can distinguish between noninvasive and invasive carcinoma based on histology; indicated for a suspicious breast mass on ultrasound or mammography.
Fine needle aspiration
Preferred tool for assessing a breast mass with a low probability of being malignant → See “benign breast conditions” for details.
FNA cannot distinguish between noninvasive and invasive carcinomas → if cytology is suspicious for malignancy, a core needle biopsy is required to confirm the diagnosis.
Surgical excision
If CNB is not feasible
Results of CNB are inconclusive
Workup of diagnosed breast cancer
Receptor testing of biopsy samples
Immunohistochemical staining for estrogen and progesterone receptor status (positive in 70% of cases)
FISH or immunohistochemical staining for HER2/neu positive (overexpression) in approx. 20% of cases
Triple-negative breast cancer = Estrogen-negative + progesterone-negative + HER2-negative
Approx. 10% of cases
Typically more aggressive, high-grade tumors
Tumor markers
CA 15-3
CA 27-29
(Axillary) lymph node status: clinically suspicious lymph nodes require workup with CNB prior to surgical management of the breast cancer
See “Management of breast cancer” below for details regarding workup of clinically nonsuspicious lymph nodes.
Further tests
Bone metastasis: see “Diagnostics” under secondary malignancies of the bone (bone metastasis).
1st: contrast-enhanced MRI (in patients with localized bone pain or elevated ALP)
2nd bone scan: if MRI detects metastatic lesion to identify additional occult lesions
Liver metastasis: abdominal CT
Lung metastasis
CXR or chest CT: usually multiple lesions, mostly unilateral pleural effusion
Thoracocentesis in the case of pleural effusion: malignant cells in the fluid (blood-tinged)
Brain metastasis: See “Differential diagnoses of brain tumors” in the article on brain tumors.
Axillary lymph node involvement suggests that hematogenic spread has already occurred!
Pathology
Non-invasive carcinoma
Invasive carcinoma
Treatment
The treatment approach primarily depends on the histopathologic classification and disease stage and involves a combination of surgical management and systemic therapy (chemotherapy, hormone therapy, targeted therapy). Patient preference for more or less aggressive management also plays a significant role in selecting the treatment approach.
Invasive carcinoma
Early stage disease
Breast-conserving therapy (BCT): lumpectomy followed by radiation therapy
Contraindications: large tumor-to-breast ratio, multifocal tumors, fixation to the chest wall, excision with negative tumor margins (> 2 mm) not guaranteed, clustered microcalcifications on imaging, involvement of the skin or nipple, a history of chest radiation
Surgical margins need to be tumor free . Otherwise, repeat resection or consider mastectomy.
Consider mastectomy for anyone unable to undergo BCT or who requests a more aggressive management.
Intraoperative lymph node evaluation
Sentinel lymph node biopsy: assesses potential lymphatic spread of cancer cells to the axillary lymph nodes ; indicated for all patients with clinically negative preoperative axillary lymph nodes
Axillary dissection : for patients with clinically positive preoperative axillary lymph nodes
Adjuvant systemic therapy
Hormone and targeted biologic therapy in all ER/PR+ or HER2+ patients
Chemotherapy in high-risk patients (see table under “Systemic therapy” below)
Locally advanced disease
Neoadjuvant systemic therapy + surgical resection (BCT or mastectomy) + axillary lymph node dissection
Followed by adjuvant systemic therapy ± radiation therapy
Advanced metastatic disease: systemic treatment followed by palliative surgery and/or radiation therapy
Gestational breast cancer
Surgery is the treatment of choice (radiation therapy is contraindicated during pregnancy)
Adjuvant chemotherapy only in the second and third trimester.
Noninvasive carcinoma
DCIS: breast-conserving therapy or mastectomy
Mastectomy plus sentinel lymph node biopsy (SNLB) if lumpectomy is not feasible (see “Contraindications” under breast-conserving therapy above)
LCIS: life-long surveillance and chemoprevention with hormone therapy (e.g., tamoxifen)
Indications for prophylactic bilateral mastectomy
A strong family history of breast cancer
Positive for mutations of BRCA 1 or BRCA 2
Patients who do not wish to take chemoprevention/hormone therapy.
Complications:
Metastatic disease: bone metastasis > liver metastasis > lung metastasis > brain metastasis
Recurrence: up to 40% are local (chest wall, lymph nodes)
Paraneoplastic syndrome: hypercalcemia of malignancy
Treatment-associated complications:
Lymphedema of the arm : results in immobility of the limb, increased risk of infection, impaired wound healing, and cosmetic disfigurement
Angiosarcoma of the breast
Sometimes referred to as lymphangiosarcoma or hemangiosarcoma, depending on whether it arises from lymphatic or capillary endothelial cells
Rare, secondary malignancy that results from chronic lymphedema in patients who underwent radiation therapy and/or lymphadenectomy after mastectomy
Presents with multiple blue/purple, macular, and papular lesions in the area of the breast, chest wall, or upper extremity
Endometrial cancer is promoted by tamoxifen therapy.
Relapse typically occurs within the first five years after completion of treatment!
prognosis
Prognostic factors
Axillary lymph node status (most important prognostic factor)
Tumor size
Patient’s age
Receptor status (ER/PR-negative and triple-negative disease are associated with a worse prognosis)
Histologic grade and subtype
HER2-positive cancers demonstrate a more aggressive tumor growth and higher recurrence rates and therefore are associated with a poor prognosis. Since the development of targeted therapy with trastuzumab, the prognosis for patients with HER2-positive cancers has improved!
Survival
Early-stage disease without lymph node involvement
10-year survival rate: 70%
Node-positive disease: high risk of recurrence
Metastatic disease: 3-year survival rate of 48–71%
Breast carcinoma prevention
Breast cancer screening
Mammography: every 2 years in average-risk women aged 50–74 years
Two views of the breast are obtained: mediolateral oblique and craniocaudal
Physical examination plays a minor role in screening for breast cancer.
If the cancerous lesion is detectable by palpation, a stage II tumor or higher (size > 2 cm) is very likely!
Mammography has greatly improved early detection of noninvasive carcinomas! While DCIS can occasionally be detected as a palpable lump, LCIS cannot be detected by clinical examination.
Protective factors:
Early first pregnancy, several pregnancies before the age of 30 years
Breastfeeding
Physical activity
Prevention in high-risk women
High risk women
BRCA1/BRCA2 mutation-positive women
Women with a first-degree relative with a BRCA1/BRCA2 gene mutation
Women who have a family history of breast cancer
Women with a history of chest radiation therapy (between age 10–30 years)
Women with personal or family history of familial cancer syndromes (e.g., Li-Fraumeni syndrome, Cowden syndrome)
Women ≥ 35 years of age with previous invasive breast cancer or carcinoma in situ
All women should be offered
Genetic counseling
Annual mammography and MRI
Prevention measures:
Prophylactic surgery
Bilateral prophylactic mastectomy
Bilateral salpingo-oophorectomy (BSO) by age 35–40 years and/or when childbearing is no longer desired
Alternative: selective estrogen receptor modulator
Tamoxifen: In high risk premenopausal women
Tamoxifen or Raloxifene: In high risk postmenopausal women
