Breast Cancer

• Tips, pearls, and rules-of-thumb  "cheat sheet"
• Overview:  overview  types of specimens obtained for diagnosis, and a brief note  about Lexington Medical Center's "5-day Detection to Diagnosis"  program...one of the most personalized breast programs in the USA  [check it out]; for pathologists: how we handle the anatomical pathology for our above program.
• About standardizing breast pathology exams and reports.
• Nomogram (computerized decision programs) sites:
  • breast: treatment factors and how to discussion of how to decide among choices of early stage breast cancer treatments [@ Mayo Clinic; click on "programs and tools"...then scroll down to Health Decision Guides" and click on "early stage breast cancer".
  • breast: how much advantage will adjuvant (a "pre-emptive strike" against possible cells still in your body) chemotherapy give...Mayo Clinic nomogram calculator (you must put your age, number of positive lymph nodes, and maximum tumor size in the formula) by clicking on "programs and tools"...then scroll down to Health Decision Guides" and click on "adjuvant therapy for breast cancer".
  • breast: how much advantage will adjuvant (a "pre-emptive strike" against possible cells still in your body) chemotherapy give...Adjuvant!online...free registration and online use.
  • breast: decision tool at MSKCC to predict pre-surgical likelihood cancer has spread to axillary lymph nodes.
• Note file on "immuno" (IHC) tissue molecular stains in breast cancer.
• Note file on serum & tissue markers: [CA27.29/CA15.3].....[HER-2/neu].
• Note file on FNA cytopatholgy.
• Note file on benign breast tumors or masses.
• Grading non-cancer, "premalignant" breast epithelial proliferations: ductal (DIN) and  lobular (LIN) neoplasia and microglandular adenosis (MGA) ; and cancer-associated ADH & CCH. And, see below.
• Note file on non-invasive breast cancer.
• Note file on invasive breast cancer types.
• Risk calculations for chances of getting breast cancer:
  •  general age-bracket (at your age) risk for breast cancer.
  •  A chart of various risk factors for breast cancer [check it out].
  •   Harvard on-line personal risk calculator.                         
  •   Women's Cancer Network on-line personal risks.
  •   genetic testing.
• Factoring in your other health problems: your doctors must consider diabetes, heart conditions, tendency to form blood clots, etc., as they decide the risks of treatments. There are electronic calculators (such as the Charlson comorbidity index...CCI) to help in this [online calculator].
• Grading  CIS and/or Invasive Breast CANCER (how bad is it?):          
  • Elston-Ellis modification of Scarff-Bloom-Richardson (S-B-R) grading system (Nottingham combined histological grade)  for invasive ductal adenocarcinoma (IDC) [check it out].
  • LeDoussal's modified S-B-R system (MSBR) for invasive ductal adenocarcinoma (IDC) [check it out].
  • grading invasive lobular cancer (ILC) [check it out].
  • Bloom-Richardson nuclear grading system for non-invasive ductal-CIS (d-CIS) [check it out].
  • Lagios nuclear grading system non-invasive ductal-CIS (d-CIS) [check it out].
  • Van Nuys grouping system for non-invasive ductal-CIS (d-CIS) [check it out].
  • Armed Forces Institute of Pathology (AFIP) system for non-invasive ductal-CIS (d-CIS).
• IHC/ISH markers:
  • estrogen receptor (ER): one can use an instrument to "count" the result or grade the findings with words (weak to moderate staining of 80% of nuclei) or interpret an Alred score (0 to 8). As to concordance, one expects ER positivity in tubular & grade I-II IDC, ILC; ER negativity in pleomorphic IDC, medullary ca., invasive micropapillary ca. , and basal-like "triple negative" ca. (which should have very high Ki67).
  • progesterone receptor (PR): about same as ER.
  • Ki67 proliferation: expect tubular ca. & classical nuclear grade 1 ILC to be 10% or less; expect "triple negative" to be 50-90% (if not, may not be "basal-like") & expect grade III IDC to be over 25%.
  • HER-2 membrane product: check concordance by seeing what your IHC does with normal internal control duct epithelium (not to "normalize" but to help evaluate whether for "overstaining" by the IHC process); expect negativity in tubular and positivity in invasive micropapillary.
• Staging Breast Cancer [ How far has it gone already?]:
  • Finding the lymph nodes:
    • (a) our lab's "intense histological processing protocol".
    • (b) our hospital's sentinel lymph node clinical protocol.
  • TNM Staging: staging criteria 5th & 6th editions...for all invasive malignancies (AJC/TNM) [check it out].
  • For ductal-CIS (Van Nuys Prognostic Index...VNPI)  [check it out]; The USC/VNPI is a new modification (scores 4-12) which takes age into consideration. 
  • Calculate your VNPI for noninvasive (CIS) cancer [go do it].
  • KATS  risk grouping predictive for lymph node metastasis...is node sampling needed [check it]?
  • imaging studies: nuclear medicine bone scans, CT's ("cat" scans), MRI, FEG, or PET scans to detect bone, node, liver, lung, brain metastases.
  • blood tests: for cancer antigen (Ag) levels...either CA15-3 or CA27.29 (they are nearly the same...two different instrument companies and two different detection reagents) and LDH (pretreatment LDH elevations may mean proliferating cancer with necrosis).
  • sentinel lymph node (SLN) biopsy issues & Is completion (your SLN was positive) node dissection needed?...decision tool at MSKCC to predict likelihood cancer has spread to other axillary lymph nodes beyond the sentinel node (therefore, go for more).
  • special blood tests: peripheral blood CTCs (circulating tumor cells).

• What about chemotherapy? Must I have it?

  • Rule (from a May 2000 Dutch journal article ): "The criterion for choosing adjuvant systemic chemo for the individual is an expected increase in 10-year survival of 5% or more."

  • the Mitotic Activity Index (MAI) [need not know lymph node status] [check it out]...your pathologist must specifically measure it if it is to be valid, & this is not a usual determination in a routine pathology report.

  • the Nottingham Prognostic Index (NPI) [must know lymph node status] [calculate it]...your pathologist must specifically measure it if it is to be valid & this is not a usual determination in a routine pathology report.

  • the Morphometric Prognostic Index (MPI) [must know lymph node status] [check it out] your pathologist must specifically measure it if it is to be valid & this is not a usual determination in a routine pathology report.

  • Cummings Prognostic Index (CPI) [need only know node status & grade...for occult node cases]: [check it out]...your pathologist must specifically measure it if it is to be valid & this is not a usual determination in a routine pathology report.

  • Uniformed Services University of the Health Sciences: cases were more likely to get cytotoxic chemotherapy if S-phase fraction elevated [if proliferation marker of any type...such as Ki67...is really elevated?] (Am. Surg. 63[4]:330-333, 1997).

  • Genomic testing of the cancer: this began in 2004 and by March 2005, the oncotypeDX $3400 test had been done on about 5 cases in our program. There are limitations.

  • Bone marrow (BM) for cancer cells: though we don't see this test performed in our area, Dr. Richard Cote & others showed that further stratification of axillary node negative patients...(1) those with cancer cells in BM and (2) those without...helped [those with cancer cells relapsed & are certainly chemo candidates].

  • Axillary lymph node immune cell status: Dr. Peter Lee @ Stanford has recently shown that testing the nodes for T4, T8, and dendritic cells gives a powerful prediction for or against relapse...a help in decision making.

  • St. Gallen 2001 risk strata for node negative patients:
    • low risk (may not need chemo) are grade I, ER and/or PR positive, not greater than 2.0CM in size, and in patients aged 35 or higher.
    • High risk are grade II or III, ER & PR negative, larger than 2.0CM and in patients younger than 35.
      
• National Comprehensive Cancer Network (NCCN) Practice Guidelines for treatment options: go to the general web site and choose "patient options". For your particular, personal case choices, you will need to know the cancer stage that your doctors believe you are currently in. Then you can see what the consensus scientific primary/initial treatment options are for that stage. Remember that your particular case may have a mitigating or complicating factor or two which would further modify these general recommendations [check it].

(posted Jan. 2001; latest update 28 January 2008)