RT Book, Section
A1 Couch, Fergus J.
A1 Weber, Barbara L.
A2 Valle, David L.
A2 Antonarakis, Stylianos
A2 Ballabio, Andrea
A2 Beaudet, Arthur L.
A2 Mitchell, Grant A.
SR Print(0)
ID 1181416445
T1 Breast Cancer
T2 The Online Metabolic and Molecular Bases of Inherited Disease
YR 2019
FD 2019
PB McGraw-Hill Education
PP New York, NY
SN 9780071459969
LK ommbid.mhmedical.com/content.aspx?aid=1181416445
RD 2024/04/25
AB Breast  cancer  is  the  most  frequently  diagnosed  cancer  in  Western  women  and  the  leading  cause  of  death  in  U.S.  women  aged  40  to  55.  Breast  cancer  is  heterogeneous  in  its  clinical,  genetic,  and  biochemical  profile.  The  large  majority  of  affected  women  present  with  a  breast  mass  or  mammographic  abnormality  as  the  only  clinically  detectable  manifestation  of  disease,  yet  approximately  30  percent  of  women  diagnosed  with  breast  cancer  go  on  to  develop  metastatic  disease  that  ultimately  is  fatal.Numerous  risk  factors  for  the  development  of  breast  cancer  have  been  identified.  Family  history  suggesting  an  inherited  component  in  the  development  of  some  breast  cancers  is  one  of  the  strongest  known  risk  factors.  It  is  estimated  that  15  to  20  percent  of  women  with  breast  cancer  have  a  family  history  of  the  disease,  with  approximately  5  percent  of  all  breast  cancers  attributable  to  dominant  susceptibility  alleles.  Two  major  breast  cancer  susceptibility  genes  (BRCA1  and  BRCA2)  have  been  identified;  others  are  being  actively  sought.Breast  cancer  may  present  in  a  preinvasive  form  or  an  invasive  form.  Treatment  depends  on  the  stage  at  diagnosis,  patient  age  at  the  time  of  diagnosis,  and  the  presence  or  absence  of  the  estrogen  receptor  in  tumor  cells.  The  prognosis  is  largely  dependent  on  the  stage  at  diagnosis.BRCA1  is  a  highly  penetrant  breast  cancer  susceptibility  gene  on  chromosome  17q21  that  is  thought  to  account  for  20  to  30  percent  of  inherited  breast  cancers.  Families  with  germ-line  mutations  in  BRCA1  have  an  autosomal  dominant  inheritance  pattern  of  breast  cancer  as  well  as  an  increased  incidence  of  ovarian  cancer.  The  mutation  spectrum  of  BRCA1  is  well  defined,  and  functional  links  to  transcription  regulation,  cellular  response  to  DNA  damage,  and  development  are  becoming  evident.BRCA2  is  a  highly  penetrant  breast  cancer  susceptibility  gene  on  chromosome  13q12–13  that  is  thought  to  account  for  10  to  20  percent  of  inherited  breast  cancers.  Families  with  germ-line  mutations  in  BRCA2  also  have  an  autosomal  dominant  inheritance  pattern  of  breast  cancer,  an  increased  incidence  of  ovarian  cancer  that  is  less  striking  that  that  with  BRCA1,  and  an  increased  incidence  of  male  breast  cancer.  The  mutation  spectrum  of  BRCA2  is  well  defined,  and  functional  links  also  have  been  made  to  transcription  regulation,  cellular  response  to  DNA  damage,  and  development.Sporadic  breast  cancers  have  been  studied  extensively  for  molecular  changes  that  may  provide  clues  to  etiology,  prognosis,  and  improved  treatment  approaches.  Growth  factors  and  their  receptors,  intracellular  signaling  molecules,  regulators  of  cell  cycling,  adhesion  molecules,  and  proteases  have  all  been  shown  to  be  altered  in  sporadic  breast  cancer.