Breast Overview

Structure and Support

Embryology

• Starting in the fourth week of gestation, ectoderm and underlying mesoderm begin the process of proliferating and differentiating into skin.

• It is during this time that the glandular component of the breast also begins to differentiate. Paired ectodermal thickenings, termed mammary ridges, develop on the ventral surface of the embryo, extend from the axilla to the groin, and later disappear except at the level of the fourth intercostal space on the anterolateral chest wall

Breast shape is dependent on numerous factors,including fat and glandular content, skin and connective tissue compliment, and muscular and skeletal shape

The borders of the breast include the clavicle

superiorly, the inframammary fold inferiorly, the sternum medially, and the anterior border of the latissimus dorsi laterally.

The breast tissue that extends laterally through the axillary fascia into the axillary fat pad is referred to as the “tail of Spence”.

The muscles associated with the anterior chest wall include the pectoralis major, pectoralis minor, serratus anterior, rectus abdominis, and the external oblique .

While primarily attached to the pectoralis

major, the breast tissue also has attachments with the serratus anterior, external oblique, and the superior portion of the rectus abdominis.

Knowledge of the muscle group are important for surgical resection and reconstruction of the breast

Intricate fascial layers derived from the superficial fascial system support the breast tissue. Breast parenchyma is fixed in placed by the superficial fascial

system. This superficial fascial system extends cephalad from the abdomen and separates into a superficial and deep layer which envelopes the breast tissue and main tains its attachment to the breast wall.

The superficial layer of superficial fascia envelopes the glandular tissue deep to the dermal layer and can be difficult to distinguish from the dermis. However, subcutaneous adipose tissue between the dermis and the superficial layer distinguish the two layers.

The deep layer of superficial fascia diverges at the level of the sixth rib, where the inframammary fold is the inferior border of the parenchyma, and sits on the deep surface of the breast just superficial to the pectoralis fascia.

Between the deep layer of superficial fascia and the pectoralis fascia is the

retromammary space filled with loose tissue that allows the breast to move over the chest wall.

Cooper’s ligaments provide numerous interconnections between the deep and superficial layers. These ligaments penetrate the deep layer of superficial fascia and invest into the breast parenchyma to the superficial layer of superficial

fascia.

The internal mammary artery, or internal thoracic

artery, is a paired artery which after arising from the subclavian artery courses along each side of the sternum.

The internal mammary perforators branch from the

internal mammary artery and enter the superior medial portion of the breast via the second through sixth intercostal spaces, and provide approximately 60% of the vascular supply for the breast.

The second and third perforators are the largest caliber of these perforating vessels and are the preferred recipient vessels for free tissue reconstruction using the internal mammary perforators.

The lateral thoracic artery, or external mammary artery, supplies the superolateral aspect of the breast. This vessel is a primary branch of the axillary artery and enters the breast after following the lower border of the pectoralis minor muscle and passing

around the lateral border of the pectoralis major muscle.

The lateral aspect of the breast is supplied by perforators from the anterolateral intercostal arteries.

The thoracoacromial artery arises from the axillary artery and divides into a pectoral branch, which descends between the pectoralis minor and major muscles. This artery supplies the superior aspect of the breast and anastomoses with the anterior intercostal branches of the internal thoracic artery and with the lateral thoracic artery.

Venous drainage of the breast is via two systems. The

subdermal venous plexus above the superficial fascia

represents the superficial system and anastomoses with

the deep system. The deep system parallels the arterial

supply, with the veins paired to their respective arteries.

Venous perforators following the internal mammary

perforators drain via the internal mammary vein to the

brachiocephalic vein, or innominate vein. The lateral thoracic veins drain via the axillary vein into the superior Vena Cava

Lymphatic drainage of the breast includes a network of both superficial and deep lymphatic drainage

Superficial lymphatic drainage originates from the periareolar lymphatic plexus, while deep lymphatic drainage originates from each lactiferous duct and lobule, and then penetrates the deep fascia of the underlying musculature.

The predominance of lymph drainage of the breast originates from the lymphatic vessels within the breast lobules which then flow to the subareolar plexus. From this plexus, lymphatic drainage takes place through several routes. Lymphatic drainage from the lateral and superior aspect of the breast courses around the inferior edge of the pectoralis major muscle and communicates with the pectoral group of axillary nodes.

From the axillary lymph nodes, lymph drains into the subclavian and supraclavicular lymph nodes. Lymphatic drainage from the medial aspect of the breast drains to the parasternal nodes, which then drains into the bronchomediastinal trunks.

There are three levels of axillary lymph nodes

Level I – lateral to the pectoralis minor

Level II – deep to the pectoralis minor

Level III – medial to the pectoralis minor

The glandular apparatus of the breast is composed of a branching system of ducts, organized in a radial pattern spreading outward and downward from the nipple-areolar complex.

Each of the major ducts has progressive generations of branching and ultimately ends in the terminal ductules or acini. The acini are the milk-forming glands of the lactating breast and, together with their small efferent ducts or ductules are known as lobular units or lobules.

The entire ductal system is lined by epithelial cells, which are surrounded by specialized myoepithelial cells that have contractile properties and serve to propel milk formed in the lobules toward the nipple. Outside the epithelial and myoepithelial layers, the ducts of the breast are surrounded by a continuous basement membrane containing laminin, type IV collagen, and proteoglycans. The basement membrane layer is an important boundary in differentiating in situ from invasive breast cancer. Continuity of this layer is maintained in ductal carcinoma in situ (DCIS). Invasive breast cancer is defined by penetration of the basement membrane by malignant cells invading the stroma.

Mammography is the main modality for initial imaging assessment of a palpable lump in women 40 years of age

or older

Palpable breast mass. Woman 40 years of age or older, initial evaluation

US breast

• The probability of a woman developing breast cancer increases with age; a woman has a 1 in 53 chance of developing invasive breast cancer from birth to age 49 years compared to a 1 in 15 chance at ≥70 years of age.
• Diagnostic mammography is indicated as the initial examination in the evaluation of a palpable breast finding for women aged 40 years and older. However, because of the theoretically increased radiation risk of mammography and the low incidence of breast cancer (<1%) in younger women, their imaging evaluation differs from that performed for older patients.
• Most benign lesions in young women are not visualized on mammography, and US is therefore used as the initial imaging modality in younger women.

Palpable breast mass. Woman younger than 30 years of age, initial evaluation

BIRADS

Craniocaudal (CC) and a mediolateral oblique (MLO) view of each breast.

Orientation

Reporting

Lexicon

Triangulation is a technique for determining if a questionable structure is genuine or superimposition of structures.

Technique

• hang the CC, MLO, and 90° lateral films (in that order) on the view box
• the nipple on each film must be at the same level
• Use a ruler and place one end over the lesion on the 90° lateral view
• place the ruler through the lesion on the MLO view on the CC, the lesion will be found somewhere along the ruler

Interpretation

Relative to its distance from the nipple, if the lesion moves down on the Lateral film or is located lower than it was on the Mediolateral Oblique film, the lesion is in the lateral aspect of the breast. However, if the lesion moves up relative to the nipple or is located higher than it was on the Mediolateral Oblique film, the lesion is in the medial aspect of the breast. If no significant change in the location is noted, then the lesion must be located in the central aspect of the breast.

• A lateral lesion will move down on the 90° lateral (remember: DOWN AND OUT)
• Medial lesion will move up on the 90° (remember: MUFFINS RISE)
• Central lesion will not move up or down but instead remain in the same position

Mnemonic

• Muffins rise: if the lesion appears in a higher position on the lateral than MLO, then it is located medially
• Lead falls: if the lesion appears in a lower position on the lateral than MLO, then it is located laterally

Localization

Video

Lexicon

Imaging

• It is useful for identifying the primary tumor in the breastIn patients who present with axillary lymph node metastases without mammographic evidence of a primary breast tumor (unknown primary tumor) or in patients with Paget disease of the nipple without radiographic evidence of a primary tumor.

• MRI useful for assessing the extent of the primary tumor,particularly in young women with dense breast tissue; for evaluating for the presence of multifocal or multicentric cancer

• For screening of the contralateral breast; and for evaluating invasive lobular cancers

• Some surgeons use MRI preoperatively to determine eligibility for breast conservation

• However, there are no high-level data showing that use of MRI to guide decision making about local therapy improves local recurrence rates or survival.

When to use?

Lexicon

• Cyst
• Fibroadeoma
• DCIS
• Invasive Intraductal Ca
• Invasive lobular Ca
• Sarcoma

Images

Procedure:

Perfromed with a 22gauge needle, an appropriately sized syringe, and an

alcohol preparation pad. The needle is repeatedly inserted into the

mass while constant negative pressure is applied to the syringe.

Suction is released, and the needle is withdrawn. The scanty fluid and cellular material within the needle are submitted in physiologically buffered saline or fixed immediately on slides in 95% ethyl alcohol.

Malignant cells/Recurrent cyst = Core needle Biopsy

Bloody fluid = Culture and Cytology

FNA

• Core needle biopsy can be performed under mammographic (stereotactic), ultrasound, or magnetic resonance imaging(MRI) guidance.
• Specimen radiography of excised cores is performed to confirm that the targeted lesion has been sampled and to direct pathologic assessment of the tissue. A mammogram obtained after biopsy confirms that a defect has been created within the target lesionand that the marking clip is in the correct position.
• Locailization
• If a malignancy is detected, histologic subtype, grade, and receptor status should be determined from the core needle biopsy sample.

Core

Excisional

• Rare: Less than 10% of patients who undergo core needle biopsy have inconclusive results and require surgical biopsy for definitive diagnosis.
• Discordant with image findings: a spiculated mass on imaging and normal breast tissue on core needle biopsy necessitate surgical excision.
• Atypical ductal hyperplasia: surgical excision reveals DCIS or invasive carcinoma in 20% of cases because of the difficulty of distinguishing ADH and DCIS in a limited tissue sample.
• Cellular fibroadenoma on core needle biopsy requires excision to rule out a phyllodes tumor.

Diagnosis/Treatment

• Papillomas located close to the nipple are often accompanied by bloody nipple discharge.
• Less frequently, they are discovered as a palpable mass under the areola or as a density seen on a mammogram.
• Treatment is excision through a circumareolar incision, may require duct excision
• Peripheral papillomas, the differential diagnosis is between papilloma and invasive papillary carcinoma.

High Yield

Abscess

• Nonlactational abscesses may be central, peripheral, or skin associated. Central abscesses are usually due to periductal mastitis.
• Peripheral abscesses may be associated with underlying disease states such as diabetes, rheumatoid arthritis, steroid treatment, and trauma.
• Lactational abscess

Mastitis

Mastitis refers to inflammation of the breast tissue with or without infection. Nonlactational mastitis may or may not be accompanied by microbial infection:

Nonlactational mastitis can include granulomatous mastitis and periductal mastitis.

• Nonlactational periductal mastitis most commonly presents in smokers. Damage to ducts may occur from toxins in cigarette smoke or local hypoxia.
• Granulomatous mastitis is a rare, benign inflammatory disease of unknown etiology. It does not increase the risk of breast cancer.
• The condition may present as a single mass or as multiple masses within the breast. Skin changes and lymphadenopathy may also occur.

Lactational mastitis can present as cellulitis with fever, pain, redness, and swelling. Reactive lymphadenopathy can also cause axillary pain and swelling.

• Lactating infections are most common during the first 4 to 6 weeks of breastfeeding or during weaning.
• Lactating infections are caused by the proliferation of bacteria, most commonly S aureus, in poorly drained breast segments.
• Differential diagnosis includes severe engorgement, galactocele, abscess, and inflammatory breast cancer.

Presentation

• Mondor disease refers to superficial thrombophlebitis of the breast, typically the anterior and lateral chest wall.
• Symptoms include a thickened palpable cord in the subcutaneous breast, and may have associated erythema and tenderness.
• Typically involves lateral thoracic, thoracoepigastric, and superior epigastric veins.

Diagnosis

• Mondor disease can occur following trauma to the breast, surgery, needle biopsy, infection, or can be idiopathic.
• Compression or direct extension of a breast cancer can also be a rare cause.
• On physical exam, a thickened, often tender, cord-like structure is seen, with skin retraction on arm abduction.
• Diagnosis can be made on physical exam; however, imaging can be done if there is concern for malignancy. Mammogram would demonstrate a beaded cord representing the thrombosed vein.

Treatment

• Non-operative, with warm compresses and NSAIDs.
• Symptoms resolve in 4-6 weeks

Mondor Disease

High Yield

Imaging

Mammography is of little help in discriminating between cysts and fibroadenomas; however, ultrasonography can readily distinguish between them because each has specific characteristics.

• Fibroadenomas are benign tumors, although neoplasia may develop in the epithelial elements within them.
• Cancer in a newly discovered fibroadenoma is exceedingly rare;
• 50% of neoplasias that involve fibroadenomas are LCIS,
• 35% are invasive carcinomas,
• 15% are intraductal carcinoma.
• When a tissue diagnosis confirms that the breast mass is a fibroadenoma, the patient can be reassured, and surgical excision is not needed. If the patient is bothered by the mass or it continues to grow, the mass can be excised.

Cancer Risk/Treatment

Phyllodes

Tumor

PHYLLODES TUMOR

• Fibroadenoma-like tumor with overgrowth of the fibrous component; characteristic leaf-like' projections are seen on biopsy
• Most commonly seen in postmenopausal women
• The current World Health Organization (WHO) working group classification recognizes three categories of phyllodes tumors: benign, borderline, and malignant.
• Based on similar outcomes data, the World Health Organization (WHO) Working Group recommends classifying lesions with overlapping features of cellular fibroadenoma and benign phyllodes tumor as fibroadenoma.
• Phyllodes tumors require complete excision with negative margins. Mastectomy is necessary only when free margins cannot be achieved without it. Involvement of axillary nodes is rare, and axillary sampling is not indicated.

High Yield

Imaging

After Imaging obtained proceed with further evaluation based on BI RADS

• Biopsy
• Aspiration of cyst

Treatment

• Adenosis is frequently associated with a proliferation of stromal tissue that produces a histologic lesion, sclerosing adenosis, which can be confused with carcinoma grossly and histologically.
• Sclerosing adenosis can be associated with deposition of calcium, which can be seen on a mammogram in a pattern indistinguishable from the microcalcifications of intraductal carcinoma.
• In many sclerosing adenosis is the most common pathologic diagnosis in patients undergoing needle-directed biopsy of microcalcifications.

Sclerosing Adenosis

High Yield

Imaging

Given a radial scar diagnosed by core biopsy, describe indications for surgery:

• Radial scars identified on core biopsy are associated with malignancy up to 25% of the time when excised.
• Surgical excision is recommended for most radial scars.
• Small, incidental radial scars diagnosed with vacuum-assisted core biopsy and concordant with imaging findings may be observed.

Treatment

Imaging

Reassurance

Treatment

A 56-year-old postmenopausal woman with no significant medical history presents to your office with a new diagnosis of ductal carcinoma in situ. The mass measures 7 mm on mammography and is positive for estrogen receptor and progesterone receptors on stereotactic needle biopsy (grade I). On physical examination there are no palpable masses or lymphadenopathy. What is your treatment plan for this woman?

A. Surgical excision

B. Surgical excision with sentinel lymph node biopsy, followed by hormonal therapy

C. Surgical excision with sentinel lymph node biopsy, followed by breast radiation and hormonal therapy

D. Surgical excision followed by hormonal therapy

E. Surgical excision followed by breast radiation and hormonal therapy

E. Surgical excision followed by breast radiation and hormonal therapy

• Ductal carcinoma in situ (DCIS) is a premalignant lesion for which surgical excision is recommended due to a 20% chance of invasive ductal carcinoma being present in the specimen.

• According to the National Surgical Adjuvant Breast and Bowel Project (NSABP) B-17 study, the standard of care for DCIS is lumpectomy and radiation, which decreased local recurrence.

• Hormonal therapy is also recommended because DCIS puts patients at a higher risk of developing invasive breast cancer.

• Sentinel lymph node is not recommended for DCIS unless the following apply: lesion greater than 4 cm, palpable mass, mastectomy, and microinvasion.

Ductal Carcinoma In Situ

• DCIS is a nonobligate precursor for progression to invasive disease.

• While the etiology and pathogenesis of in situ neoplasia remains uncertain, DCIS has become a frequently detected histologic feature of breast screening programs.

• Currently, 20% to 25% of “breast cancer” detected by mammography is DCIS alone.

• Standard of care for DCIS follows the established treatments for invasive breast cancer: complete excision of the DCIS with a clear margin (potentially followed by breast radiotherapy and endocrine therapy) or mastectomy.

Ductal Carcinoma In Situ: Diagnosis

• The diagnosis of DCIS is usually made as an impalpable lesion detected by breast screening mammography demonstrating microcalcifications and/or tissue distortion.

• More extensive DCIS may demonstrate a mass effect visible on ultrasound or present as a palpable lump.

• Magnetic resonance imaging may also be utilized to demonstrate the extent of DCIS.

• Confirmation of DCIS is best made by core needle biopsy, with radiologic confirmation of the presence of microcalcifications in the cores and subsequent histopathology.

• At the time of diagnostic biopsy, placement of one or more radiologic markers will facilitate subsequent localization for surgery.

Ductal Carcinoma In Situ: Subtype

• DCIS encompasses a spectrum of histologic subtypes all characterized by malignant-appearing cells confined to the lumen of the breast ducts. However, the appearance ranges from bland uniform cells growing from the wall of the duct or bridging the duct (papillary, cribriform) to cells filling the entire duct.

• These cells also vary in nuclear morphology, ranging from low-grade, uniform-appearing nuclei to varying size and shape and large nuclei (high grade) and also in the presence or absence of central necrosis within the duct. The combination of high nuclear grade and central necrosis is termed comedo DCIS or comedocarcinoma.

• The primary clinical relevance of the DCIS subtypes is that they may have different potential for local recurrence after breast-conserving surgery.

• The presence of high-grade cells or comedonecrosis is not an indication of any metastatic potential and does not itself warrant systemic therapy or lymph node staging but may denote a higher risk of futuren recurrence in the breast.

• This may impact on the decision to use radiation after breast-conserving surgery.

Ductal Carcinoma In Situ: Treatment

• The overall cancer-specific survival for women with DCISapproaches 100% irrespective of the subtype of DCIS and the type of treatment.

• Mastectomy is effective in DCIS, but in most cases, breast-conserving therapy (BCT) is the most reasonable and appropriate approach because it provides the same very low risk of cancer-related death.

• The primary purpose of breast surgery with DCIS is to prevent progression of the DCIS to invasive cancer and the recurrence of cancer at the original site—so-called local recurrence.

• Local recurrence can occur after mastectomy or BCT. Recurrence in the skin of the mastectomy site or on the chest wall muscle (local recurrence) is very uncommon, with a risk of about 0.5 to 3%.

• The risk of local recurrence with breast-conserving surgery is related to a number of patient factors, including age, the histologic features of the DCIS, the size of the DCIS, the extent of surgery, and the use of radiation and antiestrogen endocrine therapy.

• Younger women have a slightly higher risk of local recurrence.

Ductal Carcinoma In Situ: Treatment

• The aim of breast conservation surgery in the setting of DCIS is to achieve complete excision with negative margins and a cosmetically acceptable result.

• Current consensus guidelines recommend 2-mm margins for patients with DCIS.

• Patients with DCIS are candidates for breast-conserving surgery if the lesion is limited to one quadrant or section of the breast, if cosmetically acceptable results can be achieved given the size of the disease, and if negative margins can be achieved with lumpectomy alone.

• A total mastectomy should be considered in patients with multicentric DCIS, centrally located disease, large lesions, or in patients with inadequate surgical margins following an initial attempt at breast conservation surgery. Patients who prefer to have a mastectomy or patients in whom adjuvant radiation is contraindicated should also undergo total mastectomy.

• Patients who undergo a total mastectomy for DCIS should be offered the option of immediate breast reconstruction.

• The risk of nodal metastases in patients with DCIS is less than 3%. However, the evaluation of the axillary lymph nodes via sentinel lymph node biopsy may be considered in patients with lesions larger than 4 cm, palpable breast lesions, microinvasive disease, or high-grade disease, or in patients with suspicious axillary lymph nodes on physical examination or on ultrasound.

• All patients undergoing a total mastectomy for DCIS should undergo a concomitant sentinel lymph node biopsy because this procedure will not be possible after the mastectomy.

Ductal Carcinoma In Situ: Treatment

• Radiation therapy is currently the standard of care for patients with DCIS undergoing breast conservation therapy.

• Radiation therapy may be omitted in patients with a small foci of low-grade disease that was resected with negative margins, in patients with advanced age, or in patients with significant and extensive comorbidities.

• After lumpectomy, radiation therapy reduces the risk of local recurrence of both invasive and noninvasive breast cancer.

• Following breast conservation therapy, the decision to administer hormonal therapy, including tamoxifen, depends on the tumor hormone receptor status.

• For women with ER-positive DCIS, postoperative treatment with tamoxifen should be recommended for 5 years. This treatment has been shown to prevent both ipsilateral recurrences or new events of breast cancer.

• The standard radiation treatment is breast radiation therapy to the entire breast to a dose of about 50 Gy coupled with an additional 15 Gy administered to the site of the surgical excision (termed a boost).

• The use of whole breast radiation reduces the risk to a low level that may in some cases be reduced even further by use of an antiestrogen hormonal agent (tamoxifen or an aromatase inhibitor; see below).

• Because most local recurrences occur in the breast tissue close to the original DCIS, it is possible that radiation administered only to the affected region of the breast may be as effective as whole breast radiation therapy.

Ductal Carcinoma In Situ: Treatment

• DCIS does not spread beyond the breast; therefore, lymph node surgery is not necessary for DCIS.

• However, in 10 to 20% of cases where there are only calcifications seen on imaging and DCIS on the needle biopsy, an invasive cancer will be identified in the final surgical resection specimen.

• Because lymph node surgery may be necessary for those for whom the excision shows invasive cancer, some surgeons have advocated lymph node surgery in all women with DCIS found by needle biopsy.

• This is not appropriate in most cases because women undergoing BCT can undergo sentinel lymph node biopsy.

• Exceptions to this rule include cases where initial evaluation prior to excision shows the presence of a mass suspicious for invasive cancer on imaging or on physical examination or when the DCIS is in the axillary tail of the breast and excision may preclude subsequent SLNB because of interruption of lymphatic flow to the axilla.

• Another exception is when mastectomy is used for DCIS, SLNB is appropriate because mastectomy may preclude subsequent SLNB due to disruption of lymphatic flow and would therefore commit women to full axillary lymph node dissection (ALND) if invasive cancer were identified in the mastectomy specimen.

A 41-year-old woman with a history of scleroderma presents to your office after abnormal imaging findings on mammography. Core needle biopsy demonstrates invasive ductal carcinoma in the upper outer quadrant of the left breast measuring 7 x 7 x 6 mm. Lymph nodes are not clinically palpable. What is the most appropriate treatment plan for this woman?

A. Breast-conserving therapy

B. Segmental mastectomy only

C. Segmental mastectomy with sentinel lymph node biopsy and adjuvant radiation

D. Simple mastectomy with sentinel lymph node biopsy

D. Simple mastectomy with sentinel lymph node biopsy

• Simple mastectomy with sentinel lymph node biopsy is the most appropriate treatment option in this case.

• Current breast surgery guidelines do not list size as an absolute contraindication to breast conservation therapy, unless the mass occupies the majority of breast tissue.

• Axillary dissection may be warranted if multiple lymph nodes are positive on sentinel lymph node biopsy.

• Considering this woman’s history of scleroderma, breast-conserving therapy (BCT) is not an option due to the contraindication of radiation therapy.

• BCT would entail segmental mastectomy with sentinel lymph node biopsy and adjuvant radiation; radiation would be contraindicated with a history of scleroderma.

• Segmental mastectomy (lumpectomy) alone would be substandard care without radiation. Modified radical mastectomy is not indicated in the absence of clinically positive nodes.

Invasive Carcinoma: Classfication

• The majority of breast cancers are classified as invasive or infiltrating, characterized by the epithelial cells invading through the basement membrane of the duct or lobule.

• Properties that allow basement membrane invasion also allow the malignant cells to invade surrounding blood vessels or lymphatic channels and therefore carry the possibility of spread to distant sites.

• The majority of breast cancer arises from the ductal component of the terminal ductal lobular unit and is termed invasive ductal cancer.

• Invasive ductal carcinoma
• Invasive ductal carcinoma is the most common type of breast cancer.
• Microscopically, the lesions are characterized by cords and nests of tumor cells with varying amounts of gland formation.
• This form of carcinoma is often associated with an in situ component.

• Infiltrating lobular carcinoma
• Infiltrating lobular carcinoma is the second most common type of invasive breast cancer.
• In the majority of cases, no mass lesion is grossly evident, and the excised tissue may actually be normal or only slightly firm in consistency.
• The lesions are more likely to be mammographically occult.
• More often, multicentric and typically estrogen-receptor (ER) positive tumors are found.

Invasive Carcinoma: Prevention

• The US Preventive Services Task Force currently recommends screening mammograms every 2 years for women between the ages of 50 and 74 years of age.

• The American Society of Breast Surgeons, American Cancer Society, and the American College of Radiology recommends yearly mammography for women with average risk starting at age 40 and stopping when life expectancy is less than 10 years.

• Women with more than a 20% predicted lifetime breast cancer risk should have annual mammography and breast magnetic resonance imaging (MRI).

• For women with a significant family history of breast cancer, screening should begin 5 to 10 years prior to the youngest age at diagnosis within the family or at age 35.

• Women who are known BRCA mutation carriers should begin breast screening at 25 years of age with an annual breast MRI and mammography at age 30.

Invasive Carcinoma: Staging

A patient's prognosis is based on the stage of cancer at time of diagnosis. For the different stages, the 5-year survival rate is:

• Stage 0 or I breast cancer: typically 99%

• Stage II breast cancer: about 93%

• Stage III breast cancer: about 85%

• Stage IV breast cancer (metastatic): 27%

• The AJCC staging guidelines for breast cancer now incorporate receptor status and grade in order to provide both anatomically and prognostic staging information.

• Characteristics of a tumor, including size, nodal involvement, and the presence of distant metastases, may be determined either clinically via physical examination and imaging studies or pathologically via a biopsy.

Invasive Carcinoma: Treatment

• The general treatment algorithm involves primary surgery to the breast and regional lymph nodes with or without radiation therapy.

• Following definitive local treatment, adjuvant therapy may be considered based on the primary tumor characteristics.

• Breast-conserving therapy (BCT) involves a lumpectomy and radiation therapy.

• BCT is associated with an equivalent survival to mastectomy and gives patients a more cosmetically appealing result.

• BCT should not be recommended for patients who have multicentric disease, large tumor size in relation to the breast, history of chest wall radiation, presence of diffuse malignant calcifications on imaging, or persistent positive margins despite attempts at reexcision.

• In addition, BCT should not be considered if lumpectomy would lead to poor cosmetic outcome.

• A mastectomy is indicated in patients who are not candidates for BCT or in those who prefer mastectomy.

Invasive Carcinoma: Treatment

• SLNB is appropriate for any woman with an invasive cancer and clinically negative nodes.

• Those with clinically positive nodes are not candidates for SLNB and should have full ALND or neoadjuvant therapy.

• If there is a question about the clinical status of lymph nodes, involvement of nodes may be confirmed before surgery using ultrasound-guided needle biopsy (core-needle biopsy or FNA).

• SLNB is performed by injecting a radiolabeled sulfur colloid and/or blue dye (isosulfan blue or methylene blue) into the breast either into the periareolar skin and under the areola or around the tumor (peritumoral).
• Isosulfan blue administration has about a 0.5% risk of immediate anaphylaxis with hypotension and an occasional case with rapid onset of hives.
• Methylene blue may cause skin necrosis in a few cases. These blue dyes should not be used in pregnancy because of the potential teratogenic effects.
• Radioactive sulfur colloid is generally considered safe to use in pregnancy because the radiation dose to the fetus is exceedingly low.

American College of Surgeons Oncology Group (ACOSOG) Z0011

• If fewer than three sentinel nodes contain metastatic disease, completion axillary dissection is not indicated if adjuvant radiation therapy will be given.

• If three or more sentinel nodes contain metastatic disease, then full axillary dissection is indicated in order to maximize local control.

Invasive Carcinoma: Treatment

• Radiation to the area of the breast is necessary in most cases of cancers treated by BCT to reduce the chance of recurrence in the breast area (local recurrence).

• For those with negative axillary nodes: whole-breast radiation, with consideration of regional nodal radiation based on the size and histologic characteristics of the tumor

• For those with one to three positive axillary nodes: whole-breast radiation, with strong consideration of radiation to the infraclavicular, supraclavicular, internal mammary, and axillary lymph node beds.

• For those with four or more positive axillary nodes: whole-breast radiation and radiation therapy to the surrounding regional lymph node basins

• Radiation is also necessary for select cases treated with mastectomy.

• Postmastectomy radiation therapy is indicated for patients with a high risk of local recurrence of breast cancer.

• Patients with a high risk of such recurrence include those with tumors greater than 5 cm, involvement of the surgical margins, and disease in the axillary lymph nodes.

Invasive Carcinoma: Treatment

A 41-year-old woman presents with a right-sided retroareolar mass. On examination, she has no associated skin changes, no nipple discharge, and no axillary adenopathy. A mammogram shows a right-sided 3.2-cm spiculated mass directly behind the nipple. Core needle biopsy is significant for invasive ductal carcinoma, with estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 (HER2) negativity and a Ki67 of 72%. Germline genetic testing is positive for a pathogenic mutation in the BARD1 gene. The woman is interested in breast conservation therapy. What is the next best step?

A. Partial mastectomy and sentinel lymph node (SLN) biopsy with adjuvant radiation therapy

B. Mastectomy and complete axillary node removal to reduce the risk of recurrence of triple-negative breast cancer

C. Partial mastectomy and SLN biopsy with intraoperative radiation therapy

D. Right mastectomy and SLN biopsy and prophylactic left mastectomy because of the genetic mutation

E. Neoadjuvant chemotherapy followed by partial mastectomy and SLN biopsy with adjuvant radiation therapy

E. Neoadjuvant chemotherapy followed by partial mastectomy and SLN biopsy with adjuvant radiation therapy

• Neoadjuvant chemotherapy followed by breast-conserving therapy (BCT) is correct. In triple-negative breast cancer (TNBC), neoadjuvant chemotherapy has been associated with high pathologic complete response (PCR) rates (compared with hormone receptor–positive breast cancers).

• PCR in TNBC has significant prognostic value in that it has been associated with improved event-free and overall survival; for this reason, neoadjuvant chemotherapy is recommended in TNBC for tumors larger than 0.5 cm.

• This woman is also not an optimal candidate for intraoperative radiation given her young age and the size of her tumor.

• Although TNBC has a high incidence of recurrence, a modified radical mastectomy does not improve overall survival when compared with BCT. Furthermore, for a pathogenic mutation in BARD1 associated with TNBC, there is little evidence supporting risk-reducing mastectomies, and the woman’s risk of contralateral breast cancer should be managed according to her family history.

• Risk factors include increasing age; radiation exposure; and factors related to abnormalities in estrogen and androgen balance, including testicular disease, infertility, obesity, and cirrhosis.
• Risk factors related to a genetic predisposition include Klinefelter syn-drome (47,XXY karyotype); family history; and BRCA gene mutations, particularly BRCA2 mutations. Gynecomastia is not a risk factor.

Risk Factors

• Histologically, 90% of breast cancers in men are invasive ductal carcinomas.
• Approximately 80% are ER positive, 75% are PR positive, and 35% overexpress HER-2.
• The remaining 10% are DCIS.
• Given the absence of terminal lobules in the normal breast in men, invasive and in situ lobular carcinoma is rarely seen.

Pathology

• Most men with breast cancer have a breast mass.
• The differential diagnosis includes gynecomastia, primary breast carcinoma, metastasis to the breast from carcinoma at another site, sarcoma, and breast abscess.
• In addition to local pain and axillary adenopathy, initial symptoms may include nipple retraction, ulceration, bleeding, and discharge.

Presentation/Differential

Prognostic factors for breast cancer in men are the same as prognostic factors for breast cancer in women and include nodal involvement, tumor size, histologic grade, and hormone receptor status. Survival in men with breast cancer is similar to survival in women with breast cancer matched for age and stage.

Prognosis

• Treatment of breast carcinoma in men depends on the stage and local extent of the tumor, with treatment options similar to the options for women
• Small tumors may be treated by local excision and irradiation or by mastectomy.
• Sentinel node biopsy has been shown to be effective for staging breast cancer in men.
• Breast tumors in men more commonly involve the pectoralis major muscle, probably because breast tissue in men is scant.
• If the underlying pectoral muscle is involved, modified radical mastectomy with excision of the involved portion of muscle is adequate treatment, but it may be combined with postoperative radiation therapy.
• Adjuvant systemic therapy for breast cancer in men is the same as adjuvant therapy for breast cancer in women. Most breast cancers in men are hormone receptor positive

Treatment

Surveillance for mastectomy patients is physical examination:

• Every 3 to 4 months for the first 2 years
• Then twice annually for 5 years
• Mammograms are not ordinarily done on the postmastectomy site, however, can be considered for the contralateral breast, particularly if gynecomastia is present or physical-examination interpretation is uncertain.

Follow up

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