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Breast cancer in young women is a biologically unique disease that requirescustomized management strategies, researchers reported at the 4thIMPAKT Breast Cancer Conference, in Brussels, Belgium, 3-5 May2012. The reported findings have potentially important implications fortreatment, because breast cancer in young women is often aggressiveand diagnosed at an advanced stage, meaning the prognosis for thesepatients is often poor. Dr. Hatem A. Azim Jr., a medical oncologist from Institut JulesBordet in Brussels, and colleagues showed that breast cancer inwomen forty-years or younger is enriched with the aggressivebasal-like tumors. Moreover, these patients have a significantlyhigher risk of relapse independent of stage, histological grade,breast cancer molecular subtypes and treatment received. A subgroup analysis showed a particularly poor trend in patientswith luminal tumors, i.e. estrogen receptor positive. "While someinvestigators could refer this to poor compliance of young women tohormonal therapies, we performed another analysis in 1,188 womenwho did not receive any systemic therapy and indeed foundsignificant poor outcome in young women both in luminal-A andluminal-B tumors," Dr Azim said. Luminal-A cancers are ER+ and low-grade, while Luminal-B cancers are ER+ but oftenhigh grade. To elucidate the possible reasons behind the poor outcome in youngwomen, Dr Azim and co-workers went on to study the expression of avariety of genes in women with breast cancer to see if theycorrelated with age. They adjusted their findings to take intoaccount the size of the tumor at diagnosis, whether the disease hadspread to lymph nodes and breast cancer molecular subtype, inaddition to other variables. The researchers performed their analysis on two independentdatasets, including 1,188 and 2,334 patients, and found the sameresults in both cases. "What we found was that even after adjustment for these parameters,there are several genes and gene signatures that are significantlyassociated with age in breast cancer patients," Dr Azim explained."Some were highly expressed in young women - including stem cells , luminal progenitors, RANK-ligand (RANKL) and c-kit-- while otherswere down-regulated, such as genes related to programmed celldeath, or apoptosis." The findings show that breast cancer arising at a young age seemsto be associated with age-related biological processes, whichappear to be independent of other prognostic factors that arecommonly used by oncologists. The genomic analysis also identified a number of signaling pathwaysin the breast cancers of young women that could be potentialtargets for treatment, Dr Azim's group reports. For example, a gene signature of the phosphoinositide 3-kinasemolecular pathway was highly associated with young age. "PI3k is animportant targetable signaling pathway in breast cancer and perhapsthese results could encourage investigating its role in breastcancer arising in young women," Dr Azim said. The researchers also found that a gene called RANKL is highlyexpressed in young women with breast cancer. RANKL is known to playa vital role in the spread of cancer to the bones, and emergingpreclinical data have shown that RANKL appears to have ananti-tumor effect apart from its role in bone metastasis. "Putting all the information in context, we hypothesize thatperhaps targeting RANKL could be particularly interesting in youngbreast cancer patients," Dr Azim said. The researchers fromInstitut Jules Bordet are in fact planning a clinical trial inwhich premenopausal breast cancer patients will receive twoinjections of a drug called denosumab, which is a RANK-ligandinhibitor, one week before surgery. The aim of the study is toevaluate the effect of RANK-ligand targeting on the biology of thetumor. The study, called D-BEYOND, is expected to start in 2012 inthree Belgian centers. In other results presented at IMPAKT, the researchers investigatedthe prognostic performance of known gene expression signaturesaccording to age. "As breast cancer arising below the age of 40 is relativelyuncommon, we lack information on whether different gene signaturesprovide prognostic information in a uniform way across differentage groups," Dr Azim said. "We tested three proliferation-relatedsignatures and found that they add prognostic information in allpatients with ER+ breast cancer, irrespective of age." "This is clinically relevant as it underscores that these genesignatures could identify women below the age of 40 with ER+disease who are at a low risk of relapse independent of clinicalprognostic tools," Dr Azim explained. Commenting on the recently published study, which he was notinvolved in, Prof Bryan Hennessy, from Beaumont Hospital in Dublin,said: "Young women with breast cancer tend to have a poorerprognosis. This study provides evidence that breast cancer in youngwomen is associated with unique underlying biologic processes,highlighting important information that may allow us to designtailored therapy approaches to improve outcomes in thispopulation." Additional References Citations. We are high quality suppliers, our products such as Bangle Cuff Bracelets Manufacturer , China Custom Finger Rings for oversee buyer. To know more, please visits Pearl Necklaces For Women.
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