Every now and then, a concept catches the imagination of the medical fraternity at large, and today the catchphrase is “evidence based medicine” or EBM. The most commonly cited definition of EBM is “the conscientious, explicit, and judicious use of the current best evidence available for making decisions about the care of individual patients”.

Breast cancer is one of the most researched fields in oncology, partly because it offers scientists ample opportunities for long term studies. Secondly the very commonness of this cancer allows many disciplines to work in tandem viz. the basic scientist, the immunologist, the molecular biologist, the histopathologist and the clinical researcher. Obviously a huge volume of data on breast cancer exists in the world, but translating knowledge into wisdom, and wisdom into logical treatment decisions – this is the basis for EBM.

Evidence for Use of Different Modalities in Diagnosing Breast Cancer

1. FNAC Vs Core biopsy: FNAC is a time tested simple office procedure with a high degree of diagnostic accuracy and precision. The specificity and sensitivity of diagnostic precision lies in the range of 60% and 80% respectively. The acceptance both by surgeons and pathologists speaks of a level of comfort which allows for radical surgery on the basis of a definitive FNAC diagnosis. False-positive and false-negative diagnoses were seen in 1.7% and 7.1% of biopsy-proven specimens sampled by FNAC. The corresponding values for core biopsy were 0% and 5.7%, respectively. Core biopsy is most useful in diagnosis of sclerotic tumors.

2. Core Vs Excision biopsy – In western countries the needle core is a popular technique for diagnosis, but yet in one out of four difficult cases, the needle biopsy has to be followed by an excision biopsy before a treatment decision can be made. Examples of lesions that are difficult to diagnosis include lobular cancers, intraductal proliferations, papillary tumors, and some cellular biphasic tumors. In addition, care is needed not to mistake sclerosing adenosis and radial scar for low grade malignancy.

3. Frozen section (FS): Adequate for primary diagnosis, sentinel node sampling and occasionally for margins of resection.

a. The accuracy of primary diagnosis in experienced hands approaches 97%, always keeping in mind that some 3-5% cases will be deferred, especially when papillary lesions, mammographically diagnosed lesions, or small lesions are encountered.
b. Evaluation for margins is best reserved for closest or revised margins; and is not advocated for complete margin evaluation. The risks of over and under-evaluation by FS are real and not worth the effort.
c. Sentinel node evaluation can be effectively performed on frozen section, particularly when combined with assessment of imprint smears.

Pathological Prognostic factors in breast cancer
Prognostic factors are indicators of the inherent aggressiveness or virulence of a tumour, as well as the extent of spread. Predictive factors are aspects in a pathology report which allow the clinician to predict certain outcomes & decide upon future plans.

What is the bare minimum that must be incorporated in a pathology report?
In an attempt at disseminating information on the use of the best prognostic markers in many different organ systems, a group of eminent pathologists, clinicians and statisticians under the auspices of the “College of American Pathologists” scrutinizes all the available literature on prognostic markers. Subsequently the statement for breast cancer, published as the “College of American Pathologists Concensus Statement” has defined categories of prognostic markers. These are as follows

Category I

Factors of proven histologic importance and useful in clinical management viz
l TNM staging
l Histologic grade
l Histologic type
l Mitotic count
l Hormone receptor status
These factors hence become mandatory inclusions for a breast pathology report

Category II
Factors extensively studied biologically & clinically but whose import remains to be validated with more robust studies. The factors in this category are
l C erb B 2
l Lymphovascular invasion
l P 53
l Proliferative markers (MIB-1)

Category III
These are factors which are not yet sufficiently studied to prove their prognostic value. These include a host of tests such as

l DNA ploidy
l Microvessel density
l EGFR
l Bcl2
l p S 2
l Cathepsin D

In summary, as a matter of scientific accuracy & completion, in the present day, the pathology report is obliged to include details of the following prognostic & predictive information. Hence all reports are required to be written in a precise and complete manner.

The check list for a breast cancer report is as follows :

BREAST EXCISION SPECIMEN
l Diagnosis, to include the type of invasive carcinoma*1
l Grading* Nuclear grade (1, 2, or 3)
* Tubule formation (1, 2, or 3)
* Mitotic index (1, 2, or 3)
Composite histologic grade*2

l ‘T’ size of invasive tumour*3
l Type of in situ carcinoma (DCIS)
l Extent of DCIS (significant or not) / EIC*4 present or absent
l Size of DCIS if invasive element is absent
l Excision biopsy margins of resection*5
l Blood vessel and lymphatic embolisation 

LYMPH NODE DISSECTION
l Total number of nodes sectioned
l Number of involved nodes
Documentation of micrometastasis*6
Extension of tumour in perinodal fat
Presence of emboli in perinodal lymphatics

Hormone Receptor Status by Immunohistochemistry
Estrogen Receptor :
Progesterone Receptor :
Pathologic Stage - pT — N —

*1 Ductal vs lobular; subtype
*2 Nottingham modified Bloom-Richardson grading
*3 preferably microscopic
When DCIS is more than 25% of the invasive carcinoma component in the examined tumor sections
*4 including evaluation of base in mastectomy specimens
*5 metastatic focus in a node that measures 2 mm or less

References :
1. British Medical Association. Report of the working party on medical education. London: BMA, 1995

2. Berner A, Davidson B, Sigstad E, Risberg B.Fine-needle aspiration cytology vs. core biopsy in the diagnosis of breast lesions. Diagn Cytopathol. 2003 Dec; 29(6):344-8

3. Chinoy RF: “Guidelines for Breast Pathology Reporting” Tata Memorial Hospital” Professional Education Division 1997

4. Crowe JP Jr, Rim A, Patrick R, Rybicki L, Grundfest S, Kim J, Lee K, Levy L. A prospective review of the decline of excisional breast biopsy. Am J Surg. 2002 Oct;184(4):353-5

5. Fitzgibbons PL, Page DL, Weaver D, Thor AD, Allred DC, Clark GM, Ruby SG, O’Malley F, Simpson JF, Connolly JL, Hayes DF, Edge SB, Lichter A, Schnitt SJ. Prognostic factors in breast cancer. College of American Pathologists Consensus Statement 1999.Arch Pathol Lab Med. 2000 Jul; 124 (7): 966-78.

6. Noguchi M, Minami M, Earashi M, Taniya T, Miyazaki II, Mizukami Y, Nonomura A, Nishijima H, Takanaka T, Kawashima H, Saito Y, Takashima C, Nakamura S, Michigishi T, Yokoyama K. Pathologic Assessment of Surgical Margins on Frozen and Permanent Sections in Breast Conserving Surgery. Breast Cancer. 1995 Apr 30; 2(1):27-33