Breast Cancer Diagnosis and Techniques for Biopsy

Breast Biopsy

There has been a steady increase in the utilization of image-guided breast biopsies, compared with open surgical biopsies, for the definitive diagnosis of breast cancer. Percutaneous image-guided core needle biopsy (CNB) has an equivalent accuracy to open surgical biopsy. Specifically, for women at average risk of breast cancer, both US- and stereotactic-guided breast biopsies have average sensitivities higher than 0.97 and average specificities ranging from 0.92 to 0.99. Additionally, owing to advances in breast imaging and biopsy devices, image-guided tissue sampling has a lower risk of complications compared with open surgical biopsy; less than 1% of image-guided biopsies result in severe complications (defined as complications needing medical or surgical intervention).

Breast percutaneous biopsies utilize imaging guidance to obtain samples of breast tissue through precise needle guidance ( Fig. 13.2 ). These minimally invasive breast procedures include fine-needle aspiration (FNA) and CNBs. Conversely, open surgical biopsies include excisional biopsy (i.e., complete removal of the lesion) and incisional biopsy (i.e., partial removal of the lesion).

Prior to performing a breast biopsy, the patient’s history, physical examination findings, and radiologic imaging should be reviewed and carefully considered. The primary objective of a breast biopsy is to obtain a definitive tissue diagnosis that can effectively guide treatment and preoperative planning, as indicated. Subsequently, it is imperative to choose a biopsy technique that optimizes the likelihood of obtaining an accurate diagnosis while minimizing costs, limiting patient discomfort, and reducing the need for a repeat procedure.

Fine-Needle Aspiration

FNA obtains cytologic, rather than histologic, specimens from the breast tissue. Although still used at some breast imaging facilities, the widespread use of FNA has decreased as additional core and vacuum-assisted devices have been introduced. FNA of breast masses and lymph nodes is a safe and reliable diagnostic technique that can be performed in the ambulatory clinic setting using local percutaneous anesthesia. Compared with CNBs, FNAs have less morbidity/complications, lower cost, and faster turnaround time. Although FNA results are often immediately available following aspiration, CNBs are often favored over FNA since CNB specimens also allow for characterization of ductal carcinoma in situ versus invasive cancer and additional tumor biomarker evaluation including the estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor-2 (HER2) is typically obtained and used to guide appropriate cancer treatment. Nevertheless, there is a persistent role for FNA, primarily in the evaluation of palpable masses with a low to intermediate suspicion for cancer and in resource-constrained settings where FNA may be more feasible than CNB.

Procedure

The use of US guidance during FNA minimizes the risk of inadvertently penetrating any adjacent vascular structures. The skin overlying the palpable mass is infiltrated with a local anesthetic. Then, the breast mass is held relatively immobile by using one hand to gently, yet firmly, hold the mass in place. This procedure typically uses a 10- to 20-mL syringe and 22- or 25-gauge needle. Using real-time imaging guidance, the needle is inserted into the mass while simultaneous suction is being applied to the syringe. Inserting the needle into the mass at various angles allows clumps of cells to be dislodged from the tumor, aspirated into the syringe, and submitted for cytologic examination. Many facilities prefer to have pathology representatives available during sample collection. This allows verification that an adequate amount of tissue has been retrieved for an accurate diagnosis. Once the procedure is complete, local pressure is applied to the site. This procedure is well tolerated and the most common complication, hematoma formation, is rare.

Accuracy

The sensitivity of FNA is often >90% with a pooled sensitivity on metaanalysis of 92% (95% CI 91%–93%). False-negative results have been shown to range from 1% to 10%. It is important to note that these rates do not markedly differ from results of CNB; in one study that directly compared FNA with CNB, the sensitivity of both FNA and CNB was 97% and the diagnostic accuracy was 95% versus 96%. Furthermore, FNA has been shown to be more cost-effective than CNB without compromising diagnostic accuracy.

The diagnostic certainty of FNA is highly dependent on the experience and skill of the interpreting cytologist. Subsequently, the routine use of FNA requires local institutional expertise to ensure accuracy. Successful FNA evaluation necessitates specialized training and close multidisciplinary communication between the cytopathologist, referring clinician, and radiologist. False-positive results range from 0% to 2%, and many studies have reported a 100% positive predictive value for breast FNA. Thus breast lumpectomy may be safely performed following FNA confirmation of breast cancer. However, given the small risk of a false-positive result, caution would dictate that mastectomy should not be performed without additional tissue confirmation of malignancy.

Since false-negative rates of breast FNA range from 1% to 10%, it must be emphasized that the absence of malignant cells in the aspirate does not entirely rule out the possibility of an underlying breast cancer. A 2012 metaanalysis reported that more than a quarter of all FNA samples may result in insufficient material for diagnosis. A clinically suspicious breast abnormality with concerning imaging findings may be initially investigated with FNA. However, if the cytology results are discordant with clinical/imaging findings, then an additional definitive diagnosis must be pursued by means of CNB or surgical excision.

Cytopathology

The National Cancer Institute recommendation for the diagnosis of breast aspiration cytology has divided fine-needle aspiration biopsy findings into five categories: C1 = unsatisfactory; C2 = no suspicious features; C3 = cells suspicious but probably benign; C4 = cells suspicious but probably malignant; and C5 = definitely malignant. Clinically, category C2 is defined as negative, and categories C3 through C5 are defined as positive, which necessitates additional workup or treatment.

Biomarker evaluation for ER, PR, HER2, and other markers may be performed on fine-needle aspirate by centrifuging the cellular material and performing immunohistochemical (IHC) staining on the resulting cell block. Several studies have shown that ER and PR can be successfully evaluated on FNA alone; HER2 IHC testing, may also be obtained. However, since the tissue architecture is lost on a cellular aspirate, FNA cannot distinguish between ductal carcinoma in situ and invasive cancer. Because this determination is often critical to treatment planning, CNB may often be required to differentiate between these two diagnoses.

FNA remains the most cost-effective diagnostic procedure for the evaluation of breast masses in developing countries. FNA is minimally invasive and enables rapid onsite provisional reporting which is ideal for multidisciplinary “1-stop” diagnostic clinics. However, FNA requires a more specialized expertise and coordinated multidisciplinary approach than CNB, so this is not a feasible option at some centers. Finally, radiology imaging concordance with cytologic findings is essential, and this assessment should be performed as a routine component of each breast FNA specimen.