Case #1 Answers:
Answer 1
It is estimated 211,000 American women will be diagnosed with breast cancer
in 2003 and 40,000 will die of this disease. It is the second most common
cause of cancer death among women next to Lung Cancer. One in nine women
will develop invasive breast cancer.
Answer 2
Known risk factors include, family history of breast cancer, genetic
mutations, proliferative lesions without atypia, proliferative lesions with
atypia age at menarche, estrogen exposure, previous history of breast cancer
and radiation exposure to breast.
Answer 3
These are mutated tumor Suppressor genes and are transmitted in an autosomal
dominant manner, with high degree of penetrance. Only 5 to 6 percent all
breast cancers are associated with germline genetic mutations. They are
important since they account for the majority of the genetically related
breast cancers. Several hundred mutations have been reported within BRCA 1
and BRCA 2. They are rare, occurring in 0-1 percent of the general
population. They have been cloned and testing for them is commercially
available.
BRCA 1 gene is localized to chromosome 17
BRCA 1 gene mutation is associated with increased risk of developing Breast,
Ovarian, Prostate and Colon Cancer.
BRCA 2 gene is localized to chromosome 13. Mutations in this gene lead to
increased risk of developing Breast Cancer in men and women.
Answer 4
Usual presenting signs and symptoms of breast cancer are palpable mass in
the breast, abnormal screening mammograms, rarely nipple discharge or
inversion of nipples and pagets disease of nipple and dimpling of skin.
Answer 5
The differential diagnosis of a non-tender breast mass include, fibrocystic
disease, fibroadenoma, fas neurosis, DCIS, invasive breast cancer, and
rarely, metastasis.
Answer 6
Estrogen and Progesterone receptors are members of nuclear hormone receptor
family. These receptors are located in the cytosol of target tissues and
operate as ligand dependent transcription factors. By binding to the genes
they influence a the growth of normal and cancerous tissue.
Knowledge of receptor status of a given tumor is important for therapeutic
manipulation either by using antiestrogenic drugs, SERMS, or hormone
ablative procedures Hormonal Therapy is relatively non-toxic and produces
30-40% response rates, and at times for prolonged periods of time.
Answer 7
Important prognostic factors are: size of the tumor, nuclear and histologic
grade, favorable histologic types, nodal status. Nodal status is the most
important prognostic factor in breast cancer.
A prognostic factor is capable of providing information on clinical outcome
at the time of diagnosis independent of therapy. Such markers are usually
indicators of growth, invasion and metastatic potential.
Answer 8
A predictive factor is capable of providing information on the likelihood of
response to a given therapeutic modality.
a) Estrogen and progesterone receptors
b) Her-2 neu expression
Response to treatment and high risk for relapse
a) Cycline E
b) DNA Content
c) Proliferative Markers
d) Markers for invasion. Calhepsin D
e) Markers of angiogenesis
f) Gene expression profiling
Answer 9
Adjuvant systemic therapy is defined as administration of cytotoxic
chemotherapy or additive or ablative endocrine therapy in early stage breast
cancer, in order to eradicate or delay the subsequent appearance of
clinically occult micrometastatic disease. This translates into increase in
disease free survival and overall survival.
Answer 10
A patient with node positive disease has several options of adjuvant
Chemotherapy and are currently evolving. Can be C.M.F. standard vs I.V.
C.A.F., FAC Anthracycline and Taxanes: A.C + TAXOL. Docetatol. Herceptin +
Combination Chemotherapy. All in all adjuvant Chemotherapy is directed to
eradication micrometastatic disease, and hence decreases the recurrence rate
and prolongs survival. Premenopausal women benefit more from adjuvant
Chemotherapy than postmenopausal patients.
Answer 11
These depend on the drug combination used and are short term and long term
side effects.
Short term: Myelosupression with life threatening infections,
gastrointestinal side effects like nausea, vomiting, and diarrhea.
Alopecia, neuropathy, weight gain and fatigue.
Long term side effects: Gonadal failure, cognitive dysfunction,
cardiotoxicity. Rare secondary cancers. Myelodysoplastic syndromes and
leukemias.
Answer 12
Eradication of micrometastatic disease and thereby decrease recurrence rate,
prolong survival and possibly cure.