Updated: 4 July 2005

4.2.1 Biopsy of the Non-palpable Lesion

Usually a fine wire localization is required for the investigation of a non palpable lesion within the breast, although stereotactic core biopsies are being used with increasing frequency. In order to determine the most appropriate procedure for investigation of such lesions, it is important for the Surgeon and Radiologist to review the mammograms together to evaluate the type, site, extent and multi-focality of the abnormality. This is critical in order to determine the placement of the wire, position of the incision and the volume of the tissue to be removed in order to remove or adequately sample the mammographic abnormality.

The Surgeon should clearly mark and orient the specimens for the Pathologist. The specimen should then be radiographed to ensure that the area of concern was removed. The specimen, together with the specimen radiograph, should then be sent directly to the Pathologist who should carefully mark the resection margins, prior to cutting the specimen, so that the relationship of the lesion to the surgical margins can be ascertained. Frozen section in this context is not desirable unless the Surgeon is proceeding directly to further definitive surgery as it results in distortion of the tissue and may complicate definitive diagnosis.

If the biopsy is reported to be benign and there is doubt that the abnormal area has been completely removed, then either an immediate re-excision should be performed or the patient should return for a repeat examination and mammography 2-4 months after the operative procedure, when the breast tenderness has subsided.

4.2.2 Biopsy of the Palpable Mass

Biopsies of a palpable mass need careful review of the patient's mammograms to evaluate the extent of the lesion and possible multi-focality of calcifications elsewhere within the breast which may influence the surgical approach. Either fine needle aspiration cytology or a core biopsy is suitable as an initial diagnostic procedure if the lesion is thought to be malignant or highly suspicious for malignancy. An unequivocal positive diagnosis on a fine needle aspirate given by an experienced Cytologist has an accuracy greater than 95%. A negative fine needle aspirate or a negative core biopsy does not exclude malignancy and open biopsy is usually advisable. On occasion, lesions mammographically thought to be benign can be followed and the biopsy deferred, as, for example, in a young woman with a small lesion which is thought both mammographically and cytologically to represent a typical fibroadenoma.

Open biopsy investigation as an initial step is recommended where facilities for fine needle aspiration cytology or core biopsy are not available. Incisional biopsy may be carried out if the lesion is considered inoperable in order to provide tissue for diagnosis and hormone receptor studies. If clinically the lesion is thought to represent inflammatory carcinoma a skin biopsy should be taken in order to assess the presence of carcinoma within dermal lymphatics.

4.2.3 Preoperative Investigations

Reasonable investigations are recommended to determine the presence or absence of blood borne metastatic disease prior to definitive management. These include:

• Bilateral mammography 
• CBC 
• Liver enzymes and alkaline phosphatase 
• Chest X-ray

Bone scan is not ordinarily recommended for clinical stage T₁, T₂, N₀ cancer since asymptomatic patients are unlikely (<2%) to have a positive bone scan due to metastatic disease. For tumours greater than 5 cm, or where there are palpable axillary lymph nodes or an elevated alkaline phosphatase a bone scan should be carried out.

If the liver enzymes are elevated an ultrasound of the liver should be done.

4.2.4 Procedures for Handling Surgical Specimens

In order to provide sufficient detail for treatment planning the pathology report should include, as a minimum the following information:

• orientation, type and size of the specimen 
• size of the invasive carcinoma -- measured in millimeters 
• type of invasive carcinoma 
• grade of invasive carcinoma 
• presence or absence of lymphatic or vascular invasion 
• type, grade, and extent of in situ carcinoma -- indicating the distance the in situ carcinoma extends beyond any invasive carcinoma which may be present 
• multifocality of either the invasive or in situ component 
• relationship of carcinoma to marked margins -- measured in millimeters when close 
• number of nodes sampled and number of nodes involved 
• presence or absence and extent of extranodal spread of carcinoma in axillary fat 
• estrogen and progesterone receptor status 
• HER2/neu testing by IHC and/or FISH

A detailed, written handout with recommendations for processing specimens for pathologic assessment is available from the Vancouver Cancer Centre, Department of Pathology (1-800-663-3333) on request, or click here.

4.2.5 Partial and Modified Radical Mastectomy

The specimen removed at partial mastectomy must be oriented. At least two boundaries should be marked with sutures of different color or length so that the specimen can be oriented in three dimensions (e.g., long suture = lateral, short suture = superior).The pathologist should mark the margins of the specimen with silver nitrate or India ink and, if this has not already been done, send a portion of tumour for receptor studies. With a correctly marked specimen the pathologist will then be able to make an accurate estimate of the size of the tumour-free margin and to identify the location of any margin thought to be inadequately excised. If the margin is inadequate in a location where it is possible to improve the situation surgically then a re-excision should be carried out.

For a modified radical mastectomy, the deep aspect and axillary end should be marked for orientation so that the location as well as the number of nodes removed and involved by malignancy can be ascertained.

4.2.6 Hormone Receptor Levels and HER2 Testing

The estrogen receptor status of breast carcinoma can be determined by immunocytochemical staining of tissue specimens or of aspirates. When possible it is preferable to submit the specimens unfixed immediately to the pathologist who can select the most appropriate technique for handling each individual specimen. Progesterone receptors are also indicated as they may provide evidence of a potentially hormone sensitive tumour.

Immunocytochemical staining is the standard technique to test for estrogen receptors. It can be performed on fresh tissue, frozen tissue, core biopsies scrapings obtained from the surface of small lesions or frozen sections, and on aspirates with reliable results. Staining may also be performed on fixed tissue blocks, but the results may not be as accurate depending upon the fixative used and on delay in fixation of the specimen. In addition, estrogen receptor staining may be a useful technique in evaluating metastases in patients with unknown primaries in whom the possibility of metastatic breast carcinoma is in the differential diagnosis. For further information consult your hospital pathologist or regional pathologist as several hospitals, including the BC Cancer Agency, provide estrogen receptor staining.

HER2/neu (cerbB2) (human epidermal growth factor receptor 2) is an oncogene which is over-expressed in approximately 20% of breast cancers. Testing is done on the primary tumour and/or the recurrent tumour. HER2 overexpression is associated with a poor prognosis, possibly differences in response to different cytotoxics and is a predictor for responsiveness to Herceptin® (trastuzumab).

Accurate and reliable identification of HER2 overexpression is necessary. At this time the predominant need for HER2 testing is to determine patients who are candidates for Herceptin® which is only approved in the metastatic setting and in clinical trials in the adjuvant setting. Initial testing should be done by immunohistochemistry by experts in accredited laboratories. A quality assurance program for labs in BC has been established. The DAKO 04B5 is the choice initial IHC screen. For 2+ tests, FISH testing is of value to identify true HER2 positive over-expression which may benefit from Herceptin® therapy and may be of greater predictive value than the IHC testing. HER2 testing may also be of value in determining the type of adjuvant therapy that is used as there is some evidence that anthracyclines based regimens are superior in this setting compared to non-anthracyclines but this is still controversial. As well there are some papers to suggest that HER2 overexpression may result in some tamoxifen resistance but this is being further studied and at this time hormonal recommendations are not based on HER2 status.