Travis E. Grotz
Sandhya Pruthi
James W. Jakub
Presentation
A 40-year-old female presents with the complaint of a lump in her right breast. She has noted the mass for the past month, and it has not changed in size after her recent menstrual cycle. There is no associated pain. She has not had prior mammograms. She denies a history of breast trauma, breast surgery, or prior breast biopsies and is otherwise healthy. Her medications include oral contraceptives and multivitamins. Her mother was diagnosed with breast cancer at the age of 74 and is alive and well. On clinical breast examination (CBE), the breasts are symmetric, nipples everted, and there is no overlying skin retraction, erythema, or nipple discharge. A well-demarcated, firm, irregular mass, measuring 2 × 2 cm is palpated at the 10-o’clock position, 4 cm from the nipple. It is mobile and not fixed or attached to the overlying skin or the chest wall. She has no axillary or supraclavicular lymphadenopathy. The left breast examination is normal, and the remainder of the history and examination is negative.
Differential Diagnosis
The presentation of a breast mass is a common symptom. Although the majority of women who present with a palpable mass will have a benign finding however; as many as 10% will have an underlying malignancy. It is prudent therefore that a diagnostic evaluation be performed to exclude a cancer. The differential diagnosis includes cyst, fibroadenoma, fat necrosis, or carcinoma. Benign changes of the breast can be confused with a breast mass on self-exam including fibrocystic changes, prominent breast lobules, focal dense breast tissue, lipoma, or concentric thickening of the inframammary crease. Fibroadenomas are the most common benign breast lesions and are well circumscribed, firm, rubbery, mobile, and painless. They can present as single or multiple nodules and measure up to 5 cm in size. Cysts are round, well-circumscribed, smooth, mobile masses. They can often fluctuate with the menstrual cycle and are the result of obstruction and dilation of intramammary ducts. Cysts can enlarge and if under tension, can be painful. Both of these benign findings have classic breast ultrasound (US) characteristics. Even if the breast exam is suggestive of these benign etiologies, further evaluation with imaging and or biopsy/aspiration is required to assess clinical suspicion for a new breast mass. Fibrocystic changes are often bilateral, poorly localized, thickened symmetrical plaques of glandular parenchyma. These fibrocystic plaques are most prominent in the upper outer quadrants and can cause cyclical pain that can radiate to the axilla and also fluctuate in size with the menstrual cycle. Fat necrosis often presents with a firm, smooth, irregular mass that is occasionally tender and is associated with a history of trauma, reduction mammoplasty, or prior breast surgery. It may be associated with inflammation, pain, skin thickening, and nipple retraction mimicking carcinoma. The most common features of a primary breast carcinoma include a firm mass with poorly defined margins, associated with skin retraction, asymmetric and discrete when compared to the surrounding parenchyma and the contralateral breast. However, the clinical findings can be insidious, and one must be on guard against offering false reassurance for subtle changes without further diagnostic evaluation. Any new breast change reported by a patient typically deserves a confirmatory test before giving a benign diagnosis.
Workup
The CBE should be a standardized thorough inspection and palpation of the entire breast. During examination, both breasts should be palpated in a systematic fashion. The CBE is a diagnostic tool in the initial workup of a breast complaint. Upon inspection, the presence or absence of erythema, overlying skin or nipple retraction (including with the arms raised over the patient’s head), dimpling, nipple discharge, asymmetry, or previous scars should be noted. Assessment includes fibroglandular consistency, discrete or distinct masses that are asymmetrical relevant to the contralateral breast, and nipple and areolar abnormalities. Clinically benign lesions tend to be smooth, well circumscribed, and mobile. Clinically worrisome masses are often firm and poorly defined; fixation to the chest wall or associated with skin changes are uncommon findings, but strongly suggestive of a malignant process. However, none of these findings in and of themselves are 100% reliable.
The next step after the CBE in the evaluation of a palpable and dominant mass is to obtain diagnostic breast imaging (Figure 1). It is critical to specify these imaging studies as diagnostic and not screening in the orders; this will alert the radiologist that there is an issue of concern and is a vital component of the workup. It is important to communicate to the radiologist the location using the clock face and the distance from the nipple of the palpable mass or apply a radioopaque skin marker over the area of concern. A negative mammogram in the face of a clinically suspicious breast exam is not adequate to offer reassurance. Relying on this as the sole method of evaluation is a common cause of delayed diagnosis and litigation.
FIGURE 1 • Palpable breast mass diagnostic algorithm adapted from Pruthi S. Detection and evaluation of a palpable breast mass. (Reprinted from Mayo Clin Proc. 2001;76(6):641–648, with permission.) FNA can be used as an acceptable alternative to CNB if high-volume cytopathologists are available and comfortable with interpretation follow-up (FU).
In women <30 years of age who present with a focal area of concern, directed US evaluation is the initial preferred study, because of the low sensitivity of mammography in this setting. If the US findings are suspicious a diagnostic mammogram maybe obtained at the radiologists discretion. For women over 30 years of age, a diagnostic bilateral mammogram and directed US is indicated. The radiologist will most often obtain additional imaging that includes spot compression or magnification views. For a dominant mass, a focused exam in concert with a focused US will typically provide the most information. US can further assess the size of the mass, if it has cystic or solid features, and can often add clarity to benign lesions such as prominent lobules and focal areas of dense breast tissue. Magnetic resonance imaging is an expensive imaging modality with excellent sensitivity but low specificity that may be considered in high-risk patients with a clinically intermediate suspicion palpable mass and a normal or an indeterminate US and mammogram.
If findings on history, CBE, or imaging are suspicious for malignancy, a tissue diagnosis should be obtained. The sensitivity of fine needle aspiration (FNA) is 93% compared to 98% to 99% for core needle biopsy (CNB) and excisional biopsy. A CNB provides histologic architecture and yields more tissue for definitive diagnosis compared with an FNA, and is associated with a lower incidence of complications compared to excisional biopsy. As supported by the American Society of Breast Surgeons consensus statements, imageguided biopsies are preferred over surgical biopsies. An image-guided biopsy is as accurate as a surgical biopsy, is associated with less risk and lower cost, and has less long-term implications on cosmetics and radiographic surveillance. Surgical excisional biopsies as an initial biopsy tool are strongly discouraged as 80% of suspicious lesions following radiographic evaluation are benign and a surgical procedure can be avoided. A core biopsy that results in a diagnosis of malignancy allows one oncologic operation to be performed and affords the patient an opportunity to be well educated on the diagnosis and treatment options prior to surgical intervention. It is paramount that the radiologist, surgeon, and pathologist are in communication after the breast biopsy results to assess for concordance between the clinical, mammographic, US, and pathology findings. If the findings are discordant, a surgical excision is often recommended for histologic diagnosis. If the comprehensive imaging is negative and the palpable abnormality cannot be confirmed on imaging, then further workup is directed based on the level of clinical suspicion. For a clinically suspicious palpable lesion, a tissue diagnosis is required. If the lesion is of low clinical suspicion by exam and negative on diagnostic imaging, short-term follow-up with repeat CBE and US versus an FNA to complete the triple test can be performed. If the CBE, imaging, and cytology are consistent with a benign etiology—more commonly known as the “triple test”—this is associated with an almost 100% accuracy of a diagnosis of a benign breast lesion. FNA is only useful if there is a dedicated cytopathologist with experience differentiating benign from malignant cytologic pathology.
Diagnosis and Treatment
Our patient had a bilateral diagnostic mammogram and directed US. The mammogram revealed a spiculated lesion measuring 2 cm in the right upper outer quadrant. US confirmed an irregular, solid mass with posterior acoustic shadowing in the 10-o’clock position, 4 cm from the nipple. An US-guided CNB was performed on the same day with clip deployment. Pathology revealed a grade III invasive ductal carcinoma. The tumor cells were negative for the estrogen and progesterone receptors and did not overexpress human epidermal growth factor receptor 2 (HER2/neu). As part of the diagnostic evaluation, an US of the axillary lymph nodes (LNs) was negative for lymphadenopathy. If there was ultrasonographic suspicious features, an FNA of the LN would be performed preoperatively. Staging the axilla preoperatively by this method has been shown to be cost effective and when positive avoids an unnecessary sentinel lymph node (SLN) biopsy. If there is clinical suspicion of distant disease, a fluorodeoxyglucose-positron emission tomography scan or computed tomography should be obtained to assess for metastatic disease. If there is no clinical suspicion of distant disease, baseline preoperative laboratory and imaging tests should be those routinely required for a general anesthetic. The value of searching for occult distant metastatic disease in asymptomatic patients with clinical stage I-II disease is not beneficial.
The preoperative consultation for newly diagnosed breast cancer has become more complex and frequently requires a multispecialty approach. The discussion begins with a review of the breast pathology and breast imaging findings. The patient should be counseled about the options of breast-conserving treatment (BCT) versus mastectomy. This discussion entails understanding of the individual patient’s breast to tumor size, medical history of contraindications to radiation, patient compliance to undergo radiation, and her personal values. BCT most often is followed by whole-breast irradiation over 4 to 6 weeks, is well tolerated, and begins 3 to 4 weeks after BCT. In select situations, the patient may be a candidate for a 5-day course of partial-breast irradiation.
Patients presenting with locally advanced breast cancer and are considering BCT, are candidates for neoadjuvant chemotherapy. Neoadjuvant chemotherapy has been employed for patients with operable breast cancers who desire BCT but are not candidates based on the initial size of the tumor in relation to the size of the breast. Neoadjuvant therapy can be given in the form of systemic cytotoxic therapy or hormonal therapy, and the decision is based on the individual case. In one study, 81% of patients who were candidates only for mastectomy became eligible for BCT after neoadjuvant chemotherapy.
If the patient is interested in a mastectomy and breast reconstruction, they should meet with a plastic surgeon preoperatively to discuss their options. The discussion entails immediate-versus-delayed reconstruction as well as reconstruction with tissue expanders and implants-versus-autologous tissue. If undergoing reconstruction, some patients may be eligible for preservation of the nipple-areolar complex. The eligibility criteria are evolving and not necessarily limited to traditional criteria such as small breasts and small tumors more than 4 cm from the nipple. A radiation oncologist may be consulted preoperatively for patients who will be considered for postmastectomy radiation based on the patients age, tumor grade, size, hormonal and LN status. Invasive ductal or lobular carcinomas should be considered for axillary staging; specifically, lymphatic mapping, and SLN biopsy if the preoperative axillary US and clinical exam is negative for pathologic lymphadenopathy. Completion axillary lymphadenectomy is not advised if the SLN is negative and new evidence suggests that a complete axillary lymph node dissection (ALND) can even be safely avoided in certain node-positive situations.
Surgical Approach
Our patient has a single focus of cancer within her right breast, and the axillary US was negative for lymphadenopathy; she is wishing to proceed with BCT and SLN biopsy.
SLN Biopsy: For lymphatic mapping, most institutions utilize a dual agent method and that is what is described here. Lymphatic mapping is performed preoperatively with radiolabeled colloid injected into the breast. Peritumoral, intradermal over the lesion, or subareolar injection techniques are appropriate based on institutional preference. For axillary staging, a lymphoscintigraphy is not needed for a primary breast cancer. SLN biopsy can be performed under conscious sedation and local anesthesia; however, general anesthesia is our preferred approach. At the time of surgery, blue dye (dilute methylene blue or isosulfan blue) is injected typically in a sub- or periareolar distribution. The injection site is vigorously massaged for 5 minutes. When performed in conjunction with a mastectomy, the SLN is typically harvested near the completion of the procedure through the mastectomy incision; when performed in concert with a lumpectomy, almost always a separate incision is utilized. A small curvilinear incision is made two-finger breaths below the hair baring line in the ipsilateral axilla and taken down through clavipectoral fascia. A blue lymphatic channel is identified and traced to a SLN (Figure 2). The lymphovascular supply is clipped, and the SLN is removed and submitted for pathologic analysis. A search is made for any other SLNs. If a blue channel is not identified, then the search is guided by the gamma probe. Any blue LNs, LNs with blue lymphatic channels leading to them, LNs with counts ≥10% of the hottest node, or LNs that are suspicious by palpation are submitted as “SLNs.” It must be remembered that the goal is to find a LN with metastatic cancer if present and not to find a blue or hot node. Background radioactivity is obtained to ensure there are no remaining focal hot spots and that all SLNs have been removed. The axilla should then be palpated for any clinically suspicious lymphadenopathy prior to closure. On average, two to three SLNs are identified. Removing more than one SLN has been associated with a lower false-negative rate, stressing a search should be made to remove all SLNs and to not just stop when the first is found. This does not imply that if only one SLN is found, another normal LN in the field should be harvested. If only one SLN is found after careful search, it is appropriate to stop. In the unusual situation when there are more than five SLNs, and the hottest node was removed, it is safe to stop at five. The SLNs should be individually dissected out and removed as opposed to a section of fatty axillary tissue with the SLN and other nodes present in the section (Table 1).
FIGURE 2 • Afferent lymphatic channels stained with methylene blue dye leading to a SLN in the axilla.
TABLE 1. Key Technical Steps and Potential Pitfalls in Sentinal Lymph Node (SLN) Biopsy
Special Intraoperative Considerations
One of the potential pitfalls when performing axillary staging is failure of lymphatic mapping. Fortunately, the inability to identify a SLN is rare. Some features that have been associated with failure to identify a SLN include increasing patient age and body mass index; but of most importance is surgeon experience. When proceeding to SLN biopsy, consider prior ipsilateral breast and axillary procedures. If the patient has had a recent excisional biopsy, then the lymphatics crossing this incision will be disrupted. Injection in a subareolar location will fail to map in the setting of a recent upper outer-quadrant surgical scar. In this case, intradermal injection on the axillary side of the incision would be prudent (Figure 3). Other breast operations (augmentation, reduction, surgical biopsies) and time from prior surgery need to be considered. Subareolar injection will reliably map the breast in cases of a primary tumor and allow consistent axillary staging. However, in a patient with prior breast cancer treatment, if attempting to map a recurrence or new primary in the same breast, we strongly favor a peritumoral injection with imaging to identify aberrant drainage outside the axilla, which is much more common in this situation. Mapping failures are also much more frequent in this scenario and predictive factors include extent of axillary surgery and prior radiation therapy that can ablate the lymphatic drainage. The standard answer for failed mapping of a primary breast cancer is to perform an axillary lymphadenectomy.
FIGURE • (A) Lymphatic mapping of primary breast cancer using a subareolar injection technique (B) Lymphatic mapping of primary breast cancer after a previous excisional biopsy. The injection is intradermal on the axillary side of the incision (C) Lymphatic mapping of recurrent breast cancer using a peritumoral injection technique.
Postoperative Management
SLN biopsy is typically an outpatient procedure when combined with a lumpectomy. We also utilize a same-day outpatient mastectomy protocol for our unilateral cases without reconstruction. Postoperatively, the patient is seen back in the clinic to assess wound healing and review the final pathologic results. The exam is focused on cellulitis, wound infection, seroma, hematoma, flap necrosis, and early lymphedema (extremity or breast). We attempt to coordinate a same-day postoperative visit with medical oncology, radiation oncology, and lymphedema clinic if a complete ALND was performed. A multidisciplinary team is utilized to discuss the risks and benefits of adjuvant treatment, including adjuvant systemic and hormonal therapy and radiation.
An individualize approach is the preferred method to determining the role of adjuvant therapy. Simplistic approaches such as tumor size >1 cm or node-positive disease are no longer the only factors to consider when deciding on adjuvant therapy options. In the era of targeted therapies and individualized medicine, patients and their medical oncology team together participate in the decision-making process. The patient should be informed of her risk of recurrence and death with and without adjuvant therapy as well as potential short -and long-term toxicities of treatment. The tumor biology (predictive markers) as well as the tumor size, node status (prognostic factors), and patient’s life expectancy without cancer death are factors that are considered when deciding who should receive adjuvant systemic therapy. Oncotype DX® can be a useful tool, and after hormonal status, it is one of the first tests employed as part of the available individualized tools to help identify patients who may be able to avoid chemotherapy. Oncotype DX® is introduced into the assessment postoperatively for postmenopausal, estrogen-receptor (ER)-positive cases with borderline tumor characteristics to assess the benefit of chemotherapy. It should only be ordered after thoughtful discussion if the results will influence the treatment decision and as a rule; therefore, should be ordered by the individual who will utilize the results to alter treatment decisions. Patients with triple-negative tumors (ER negative, progesterone-receptor negative, and HER2/neu negative) will likely be offered adjuvant systemic chemotherapy. Postmastectomy radiation has been shown to improve survival and decrease recurrence risk in patients with ≥4 metastatic LNs, extracapsular extension and ≥5 cm primary tumor. It is being utilized with increasing frequency in the young, even single node-positive patient. This is an area in flux, especially in regards to the patient with locally advanced disease who has a complete response to neoadjuvant therapy.
After BCT, a diagnostic baseline mammogram of the treated breast is obtained 6 months after breast irradiation and then annually thereafter; CBE is scheduled every 4 to 6 months. After mastectomy with or without reconstruction, a chest wall exam and CBE of the unaffected breast is scheduled every 4 to 6 months and a mammogram annually of the unaffected breast.
TAKE HOME POINTS
· Most palpable masses are benign; however, all patients regardless of age presenting with a palpable breast mass require an evaluation to exclude or confirm malignancy.
· Tissue diagnosis with CNB is often indicated unless the mass can clearly be attributed to an objective benign etiology.
· Concordance between the CBE, breast imaging, and CNB is of utmost importance in determining recommendations for further surgical excision and follow up.
· CNB provides preoperative histologic assessment and in most cases allows a one-stage surgical procedure. CNB has a high degree of accuracy as well as identifying benign lesions that can be followed safely.
· Excisional biopsy as a first step approach to a breast mass should be dissuaded.
· All excised breast specimens should be oriented.
· Preoperative assessment of the axilla with US and clinical assessment. If suspicious, FNA is useful, and if it confirms malignancy, ALND is performed.
· Remove only SLNs while preserving lymphatics and other neurovascular structures.
SUGGESTED READINGS
Barton MD, Elmore JG, Fletcher SW. Breast symptoms among women enrolled in a health maintenance organization: frequency, evaluation, and outcome. Ann Intern Med. 1999;130(8):651–657.
Pruthi S. Detection and evaluation of palpable breast mass. Mayo Clin Proc. 2001;76(6):641–647.
Pullyblank AM, Davies JD, Basten J, et al. Fat necrosis of the female breast - Hadfield revisited. Breast. 2001;10(5): 388–391.
Tan PH, Lai LM, Carrington EV, et al. Fat necrosis of the breast - a review. Breast. 2006;15(3):313–318.
Warren RM, Crawley A. Is breast MRI ever useful in a mam-mographic screening programme? Clin Radiol. 2002;57(12): 1090–1097.