295EGFR and the ER are the most dangerous combination of molecules
overproduced in breast cancer. When both are overfunctioning, patients are resis-
tant to therapy and die quickly of disease progression. A study has shown how the
master gene called SRC-3 (steroid receptor coactivator 3) not only enhances
estrogen- dependent growth of cancer cells by activating and encouraging the tran-
scription of a genetic message into a protein, it also sends a signal to the activating
enzyme called FAK (focal adhesion kinase) found on the cell’s membrane to pro-
mote cell motility or movement, which is a key element of cancer spread or metas-
tasis (Long et al. 2010 ). Overexpression of SRC-3 is found in two-thirds of breast
cancers. This study shows that SRC-3 can produce an alternative form of its coacti-
vator protein – a shorter form that is missing the part of the protein (exon) that
keeps it in the nucleus. With that portion gone, it leaves the nucleus and goes into
the cytoplasm and travels to the membrane, where the enzyme PAK1 (p21-acti-
vated kinase 1) phosphorylates SRC-3, enabling it to function at the membrane.
Her2 Testing in Breast Cancer as a Guide to Treatment
The information provided by a personal genetic test might be of real value in iden-
tifying the woman whose risk for breast cancer or other cancers is likely to be
amplifi ed by oral contraceptives. Depending on the mutation, oral contraceptives
can increase the risk of breast cancer and may also fail to protect against ovarian
cancer. Thus, a positive test for certain genetic mutations means that the strategy of
using oral contraceptives to reduce the risk of ovarian cancer should be abandoned.
In contrast, a woman worried about ovarian cancer who does not have one of these
hereditary contraindications could then take oral contraceptives without danger of
precipitating a known hereditary breast cancer.
Women with a family history of breast cancer also have the option for prophylac-
tic breast removal, which reduces the breast cancer risk by 90 %. Chemoprevention
with tamoxifen or other agents is another option. The goal is to make chemopreven-
tion as effective as prophylactic mastectomy.
There is evidence that some of the gene mutations in breast cancer are relevant to
treatment. The human epidermal growth factor receptor-2 (HER2) gene also known
in avian species as c-erbB-2 (avian er ythro b lastic leukemia viral oncogene homolog
2) or in the rat as neu ( neu roblastoma oncogene) is amplifi ed in 20–30 % of breast
cancers. HER2 gene amplifi cation and HER2 overexpression occur early in the
development of breast cancers and are found in a high proportion of ductal carcino-
mas in situ (DCIS), non-invasive cancers that generally do not give rise to metasta-
ses. In DCIS, HER2 overexpression is found specifi cally in poorly histologically
differentiated disease and not in well-differentiated cancers. HER2 expression is
associated with response to trastuzumab (Herceptin) and its lack with resistance to
therapy. In a randomized trial, 1 year of treatment with trastuzumab after adjuvant
chemotherapy signifi cantly improved disease-free survival among women with
HER2-positive breast cancer (Piccart-Gebhart et al. 2005 ). The randomized, con-
trolled Mammary5 trial by the National Cancer Institute of Canada showed that
Personalized Management of Cancers of Various Organs