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.