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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:
- 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/serum markers:
proper 10% NB formalin fixation is critical to accuracy & reproducibility; >6 hr but aim for no more than 48.
- estrogen receptor (ER): alcohol fixative contact prior to formalin fixation blunts nuclear IHC marking; one can use an instrument to "count" the result or grade the findings with words (weak to moderate staining of 80% of
nuclei) or render an Allred score (a sum of 0 to 8, weakest to
strongest expression of degree of genetic penetrance of this steroid hormone receptor) by adding a digit for the appropriate percentage range of positive nuclei plus
a digit for the estimated average intensity (1-3+) of staining of nuclei.
Allred schematic parameters, HERE. (D. Craig Allred, Modern Path. 11(2):155-168, 1998)
ER Allred scoring, summing the below 2 components:
- percentage expressing...staining, points: none = 0; <10% = 1 point; 10%-1/3rd = 2 points; 1/3rd-2/3rds = 3 points; 2/3rds-100%
- intensity average of expression, points: trace-1+, mild on average = 1 point; 2+, moderate on average = 2 points; & 3+, strong on average = 3 points. There is nearly always a range of 1-3+ which we have to "average".
- progesterone receptor (PR): about same as ER.
- Ki67 proliferation: the rate drops with delay in fixation & alcohol fixative contact prior to formalin fixation blunts nuclear IHC marking; 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: fixation delays cause false positive IHC marking; 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. HER-2 page & details HERE.
- concordance: assessment: 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).
- serum markers: circulating HER-2, ca125, & ca19.
- Staging Breast Cancer [ How far has it gone already?]:
- Finding the lymph nodes:
- TNM
Staging: staging criteria 5th & 6th editions...for all invasive malignancies (AJCC/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).
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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.
- On-line riskiness or prognostic calculator simulating genomic portrayal but using H&E and IHC: we can use the NPI, the Pittsburgh formula, and common sense (all based on case-specific intent & meticulous dissection and observation, for a case-specific comment in the pathology report of the completely excised cancer and sentinel nodes, HERE.
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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 addition 27 September
2009) |
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