Catherine E. Pesce
Lisa K. Jacobs
Presentation
A 54-year-old female with a history of hyperlipidemia presents for her annual mammogram. She has never had an abnormal mammogram in the past, but she does have a family history of breast cancer in her mother who died in her 70s. On breast exam, there are no masses palpable in either breast or axilla. She does her own self-exams regularly. On review of her mammogram, she is found to have new calcifications in the upper outer quadrant of the right breast.
Differential Diagnosis
While calcifications can be overt invasive carcinoma, several other benign and premalignant lesions of the breast must also be considered.
· Sclerosing adenosis is a proliferation of the stroma and the smallest tubules within the terminal duct-lobular unit. It may mimic carcinoma clinically, radiologically, and histologically. The presence of myoepithelial cells confirms the benign nature of the lesion.
· Atypical lobular hyperplasia is a proliferation of the epithelium lining the lobules and is associated with an increased risk of future carcinoma.
· Ductal hyperplasia is proliferation of the ductal epithelial lining cells and may be of the usual or atypical type. It may have varying degrees of risk for future cancer.
· Fibrocystic breast disease is the single most common disorder of the breast. The condition is diagnosed frequently between the ages of 20 and 55 and decreases progressively after menopause. It encompasses a group of morphologic changes that often produce palpable lumps and are characterized by various combinations of cysts, fibrous overgrowth, and epithelial proliferation.
· Columnar cell change involves dilated terminal duct-lobular units, which are lined by uniform, ovoid-to-elongate, nontypical columnar cells, and these frequently exhibit prominent apical snouts. If associated with atypia, it is often associated with atypical ductal proliferations and in situ carcinomas.
· Lobular carcinoma in situ (LCIS) is a marker for increased risk of developing invasive carcinoma. Risk is equal for both breasts, and subsequent carcinoma may be either ductal or lobular.
· Ductal carcinoma in situ (DCIS) consists of malignant cells confined within the basement membranes of ducts without invasion of the surrounding stroma.
Workup
When obtaining the history from the patient, certain risk factors must be obtained including the patient’s age, history of pain, menstrual history, any skin changes over the breast, changes in the nipple-areolar complex, presence or absence of nipple discharge, personal history of previous masses or biopsies, and family history of breast cancer.
On physical exam, pertinent findings include the location of the mass, size, mobility, tenderness, fluctuance, any skin changes, nipple discharge, prior scars, and/or lymphadenopathy in the axillary, supraclavicular, or infraclavicular basins.
Mammography is the best screening test for the early detection of breast cancer for most women (Figure 1). Ultrasound is currently not used for screening but is an excellent diagnostic tool for further evaluation of an abnormal mammogram or clinical breast complaint. MRI is used for screening women at high risk for breast cancer and to evaluate the extent of disease in the ipsilateral and contralateral breast in a patient with a new diagnosis of breast cancer. MRI is superior to mammography and ultrasound in determining the size of the tumor, the presence of multifocal or multicentric disease, and the presence of contralateral disease.
FIGURE 1 • Mammographic image of calcifications
Palpable breast lesions are amenable to biopsy by fine needle aspiration (FNA), core biopsy, or surgical biopsy techniques. Fine needle aspirations can be performed in the office by either the surgeon or the pathologist. Proper and rapid fixation is imperative on an FNA specimen, and if the surgeon is to perform the procedure in the office, coordination with and assistance from the laboratory are important. Needle core biopsy offers greater sampling accuracy than FNA because the architecture of the area of concern is preserved, and this allows the pathologist to assess whether invasion is present. The National Comprehensive Cancer Network (NCCN) guidelines now recommend core biopsy before surgery.
Biopsy of nonpalpable breast lesions requires an image-guided biopsy technique. Many modalities exist to biopsy these lesions including stereotactic biopsy, ultrasound-guided biopsy, MRI-guided biopsy, and surgical excisional biopsy with image localization. Needle or wire localization of an image abnormality is the most common method for directing the surgeon to the target lesion. After needle placement, a mammogram is performed in the medial–lateral view as well as the cranial–caudal view to provide the operating surgeon with a three-dimensional location of the lesion. The surgical incision should be placed as close to the lesion as possible, while still trying to create an incision that can be incorporated into a mastectomy incision if that proves necessary in the future. The dissection is then performed down to the wire and along its course to the site of the lesion (Figure 2).
FIGURE 2 • Needle localization under ultrasound guidance
After a biopsy is complete, the pathology results must be compared to the radiographic and physical examination findings. If the pathologic diagnosis cannot account for the other findings, then this biopsy is considered discordant and should either be repeated or excisional biopsy should be done. This involves the complete removal of the entire lesion.
Diagnosis and Treatment
The primary surgical options for the breast are mastectomy or breast conservation. Mastectomy has historically been indicated for tumors larger than 5 cm. A more patient-specific criterion is applying mastectomy when the tumor is large for the size of the remaining breast and when an oncologically acceptable lumpectomy would not leave a cosmetically acceptable outcome.
For the patient at hand, DCIS is the leading diagnosis and breast conservation would be appropriate. It must be emphasized that when breast conservation is performed, radiation is required postoperatively to achieve local recurrence rates similar to mastectomy. Relative contraindications to breast conservation include tumors >5 cm, large tumor-to-breast-size ratio, and pregnancy. Absolute contraindications include T4 tumors, multicentric disease, collagen vascular disease, previous history of breast radiation, and inability to access radiation therapy.
Sentinel lymph node biopsy is the initial axillary staging procedure of choice for women with clinically node-negative invasive breast cancer. It should be considered in women undergoing mastectomy for DCIS. Patients with micrometastases <0.2 mm on sentinel node biopsy are considered node negative (N0mic) and should not be considered for completion dissection or adjuvant chemotherapy based on their nodal status. Patients with metastases larger than 0.2 mm should continue to be treated as node positive and formal axillary lymph node dissection should be discussed.
Surgical Approach
The same surgical principles of the breast are maintained during excisional biopsy, partial mastectomy, and mastectomy.
During excisional biopsy and partial mastectomy, the incision is placed along Langer lines for the best cosmetic result. If possible, a periareolar incision should be used if the lesion is centrally located because the scar then blends in with the pigment change. In the lower half of the breast, radial incisions for malignant lesions are usually used. Even though the breast may be slightly narrowed by a radial incision in the lower half of the breast, incisions along Langer lines in the inferior pole can cause more cosmetic deformity by shortening the distance between the areolar complex and the inframammary fold. A biopsy, as opposed to a partial mastectomy, has the surgical goal of obtaining a diagnosis by removing the lesion while minimizing excessive tissue loss. Therefore, wide margins are not appropriate for a diagnostic procedure. During partial mastectomy, however, a rim of surrounding normal tissue needs to be excised.
Mastectomy is usually required for women with multiple tumors in the same breast, diffuse malignant-appearing calcifications, T4 tumors, women who cannot receive radiation therapy, or positive margins after attempts at breast conservation. When positive margins occur after partial mastectomy, repeat local excision can be attempted. However, if margins remain positive when as much breast tissue as possible has been removed, mastectomy is required.
During mastectomy, the borders of the breast must be appreciated. These include the clavicle superiorly, the lateral border of the sternum medially, the latissimus dorsi laterally, and the inframammary fold inferiorly. All breast tissue, the nipple-areolar complex, and the fascia overlying the pectoralis major are removed, but the muscle is left intact.
When immediate reconstruction is planned, a skin-sparing mastectomy is preferred. This procedure involves performing an oncologically sound operation while leaving as much skin as possible. It includes removal of the nipple-areola complex, but some surgeons are pushing that boundary by using methods to preserve even the nipple and still reporting low local recurrence rates.
Sentinel lymph node biopsy entails the injection of technetium-99 m and/or isosulfan blue dye (Lymphazurin) in the breast. Nodal excision is typically performed through a small axillary incision, posterior to the lateral border of the pectoralis major muscle. Preoperative scanning with the gamma probe is often helpful in planning the incision. The incision should be easily incorporated in an incision for a subsequent axillary lymph node dissection. Nodes stained blue or with evidence of radioactivity on the gamma probe are excised intact and sent for pathologic review. In addition, nodes that are palpably firm or enlarged should also be excised. The procedure is considered complete after scanning with the gamma probe fails to reveal further radioactive counts >10% of the highest count detected (Table 1).
TABLE 1. Key Technical Steps and Potential Pitfalls
Special Intraoperative Considerations
Allergic reactions to the blue dye can happen in 1% to 2% of patients ranging from urticaria, blue hives, pruritis, bronchospasm, and hypotension. Allergic reaction should be considered in any patient experiencing hypotension in whom blue dye was used and is readily managed with fluid resuscitation and short-term pressor support. A spurious decline in pulse oximetry readings occasionally occurs after injection of blue dye and does not represent hypoxemia.
When a sentinel node cannot be located via localization of blue dye or radioactivity or positive nodes are identified, a formal axillary lymph node dissection is usually recommended. This involves en bloc resection of the level I and level II lymph nodes. The axilla is anatomically defined posteriorly by the subscapularis and latissimus dorsi muscles, medially by the chest wall and the overlying serratus anterior muscle, laterally by the skin and subcutaneous tissue of the underarm area, and superiorly by the axillary vein. The fat pad defined by these areas is excised leaving the axillary vein, long thoracic nerve and the thoracodorsal nerve, artery, and vein intact.
Postoperative Management
Surveillance of breast cancer survivors is an integral part of their care, and its importance is growing with the increasing number of breast cancer survivors. Current standard of care for surveillance in patients with treated breast cancer constitutes scheduled history, physical examination, yearly mammograms, and breast self-exams. There is no good evidence supporting routine systemic imaging or laboratory testing such as tumor marker levels in breast cancer survivors.
Patients should be referred to genetic counseling if any of the following risk factors are present: Ashkenazi Jewish heritage, personal or family history of ovarian cancer, any first-degree relative diagnosed with breast cancer before age 50, two or more first-degree or second-degree relatives diagnosed with breast cancer, personal or family history of breast cancer in both breasts, and history of breast cancer in a male relative.
Postoperative management after breast surgery includes referral to medical and/or radiation oncology as is deemed appropriate. All women receiving breast conservation will be followed with radiation therapy. Adjuvant chemotherapy statistically can benefit most women with local-regional breast cancer, but the absolute benefit of chemotherapy must be balanced against the absolute risks of treatment to determine whether this intervention is worthwhile. All women with hormone receptor positive disease should be counseled regarding the benefits of antiestrogen therapy.
TAKE HOME POINTS
· One in 8 women will experience breast cancer in her lifetime, and 1 in 33 women will die of the disease.
· While calcifications can be overt invasive carcinoma, several other benign and premalignant lesions of the breast must also be considered.
· Mammography is the best screening test for the early detection of breast cancer for most women.
· Palpable breast lesions are amenable to biopsy by FNA, core biopsy, or surgical biopsy techniques, while biopsy of nonpalpable breast lesions requires an image-guided biopsy technique.
· The primary surgical options for the breast are mastectomy or breast conservation.
· When breast conservation is performed, radiation is required postoperatively to achieve local recurrence rates similar to those with mastectomy.
· Surveillance of breast cancer survivors should follow a care plan that includes the patient’s surgeon, radiation and medical oncologists, as well as the primary care provider.
Acknowledgments
No funding was provided in this publication.
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