BRCA gene & Breast cancer

BRCA- Genes

In the case of breast and ovarian cancer as subset of affected individuals might be accounted for by dominantly inherited high penetrance susceptibility genes and two of these genes have been identified by positional cloning . BRCA 1, located on chromosome 17 , is capable when mutated of producing a high risk of breast cancer and also of ovarian cancer  Roughly  1 in 500  women carries a germline BRCA  1 mutation often giving rise to a  strong family history . Men with BRCA 1 mutations may have a modestly increased risk of prostate cancer. Mutations in BRCA 1 are  responsible for 50% of all inherited breast cancer cases. There is an array of mutational heterogeneity described for BRCA  1 as is often the case for genetic disorders. An exception is the Ashkenazi Jewish population . Mutation in another gene on chromosome 13, BRCA 2, also confer a high risk of breast cancer and men with BRCA 2 2 mutations are also prone to develop breast cancer . BRCA 2 accounts for 70% of those cases of breast cancer which are not caused by BRCA 1. The frequency of BRCA 2 mutations is estimated to be individuals without germline alterations in BRCA 1 or BRCA 2. Hereditary factors may still contribute to a significant fraction of these but those factors must be weaker and therefore more difficult to discern. One such factor may be the heterozygous state for mutations in the ataxia telangiectasia gene at 11q22. Such individuals have as much as a four to five fold increased risk of breast cancer and are likely to represent about 1 percent of the population.

CA 19.9

CA 27.29

CA 27.29 is an epitope on the protein core of the MUC-1 mucin glycoprotein  . CA 27.29 levels may be used in conjunction with other procedures for early detection of recurrence in women previously treated for stage II and stage III breast cancer and for therapeutic monitoring of patients with metastatic breast cancer. CA 27.29 levels can also be elevated in cancers of the colon stomach kidney lung ovary pancreas  uterus and liver . First trimester pregnancy endometriosis ovarian cysts benign breast disease , kidney disease and liver disease  are noncancerous conditions that can also elevate CA 27.29 levels.

CA 72.4

CA 125

This is a cell surface glycoprotein  present on 80 percent of nonmucinous  ovarian carcinomas. It is also useful for residual disease detection in patients with epithelial ovarian cancer. Serum studies have correlated increasing CA 125 levels with malignant disease and poor therapeutic response . Decreasing levels on the other hand are associated with a favorable therapeutic response . Overall CA125 levels correlate with disease in 87% of individuals. Elevated post treatment CA 125 levels  35 U/mL were found to be indicative of residual ovarian tumours possibly negating the need for a second look exploratory laparotomy. Low levels do not rule out the presence of residual  disease patients should still receive regular general physical and pelvic examination . CA 125 is also elevated in adenocarcinoma of cervix endometrium gastrointestinal tract pancreas lung breast colon in menstruation and pregnancy. It is also elevated in about 265 cases of benign ovarian tumours and 66% cases of non neoplastic conditions like endometriosis adenomyosis fibroids and acute salpingitis. CA 125 is useful to monitor  the response of treatment and if elevated suggests recurrence in women with ovarian cancer. Approximately half of women with metastatic ovarian cancer have an elevated CA 125 level.

Carcino- Embryonic Antigen

CEA is a cell surface glycoprotein that is useful to monitor patients with persistent recurrent or for metastatic colon cancer. Reported to be positive in 70% cases of colorectal carcinoma , 55% cases of pancreatic carcinoma , 50% cases of gastric cancer, 45% cases of lung cancer , 40% cases of uterine cancer and 25% cases of ovarian cancer. Serum CEA levels are also useful in monitoring the treatment of metastatic breast cancer. CEA elevations have also been reported in benign disorders like alcoholic cirrhosis hepatitis ulcerative colitis ,Crohn’s disease and occasionally in healthy smokers , CEA is neither organ specific nor tumour specific hence CEA levels should not be used for the detection of early cancers. Pre operative CEA levels should be used for predicting prognosis because the level of elevation correlates with the tumour mass . In patients with CEA positives colon cancers. The presence of elevated CEA levels 6 weeks after therapy indicates residual disease. CEA  is useful for detecting recurrence of colon cancer increased levels may precede clinical evidence of recurrence by as much as 6 months. The sensitivity for detecting recurrence is 97% in patients whose CEA was elevated preoperatively , but only 66% in those with normal preoperative levels . Individuals who smoke may have higher  baseline levels  than the non smokers.

Human Chorionic Gonadotropin

Hcg is a glycoprotein composed of two dissimilar subunits alpha and beta subunits. The alpha subunits of hcg, FSH, LH and TSH are nearly identical but the beta subunit is unique in its immunological and biological properties . Patients with gestational trophoblastic disease produce concentration of hcg equal to or exceeding levels produced in normal pregnancy for similar gestational age. The level of hcg fails to plateau at the end of the first trimester in these cases and continues to rise in proportion to in increase in trophoblastic cell mass. Thus beta hcg levels are useful for diagnosing GTD . After evacuation of the uterus quantitative beta hcg titers for one year. If hcg titers plateau or rise indicating persistent GTD a further clinical workup is necessary to rule out metastatic disease. The ratio  of free beta subunit of hcg to total hcg is valuable in the evaluation of GTD. The free beta hcg/ total hcg ratio is higher in GTD than in normal pregnancies. This ratio is lowest in Patients with hydatiform mole intermediate in invasive mole and highest in choriocarcinoma.

Beta hcg titers are extremely useful in the diagnosis and treatment of testicular tumours. They contribute greatly to the diagnosis immunohistochemical classification ,staging and follow- up of these tumours. About 50-90% cases with nonseminomatous tumours show elevated levels f beta hcg . this test is used in the evaluation of testicular masses in the staging of testicular germ cell tumours and in monitoring the response to therapy. Plasma levels of beta hcg are elevated in all patients with choriocarcinoma one third patients of embryonal carcinomas and teratocarcinomas and rarely in seminomas. Patients with seminoma and elevated beta hcg have a less favourable prognosis than those with seminoma with normal beta hcg titers . False positive results occur in men with solitary testis.

Beta hCg can serve as tumour marker for various ovarian germ cell tumours like choriocarcinoma endodermal sinus tumour embronal carcinoma nd dysgerminoma . Serial quantitative beta hCG concentrations are helpful in monitoring patients for evidence of persistence or recurrence after chemotherapy or surgery