title: Can a phenotype for recessive inheritance in breast cancer be defined?
abstract: While a dominant inheritance of breast cancer (vertical inheritance) is well known, less is known about a possible recessive inheritance (horizontal inheritance). In a clinical series of 1676 breast cancer patient's family history was scored as vertical (grandmother-aunt-mother-sister-daughter) or horizontal (sister-sister) and related to histopathological tumor type, presence of germline mutations, bilaterality, multifocality, screening, parity, hormone replacement therapy (HRT) use and age at diagnosis. Prognosis was estimated by also adding tumor size, lymph node status, distant metastases and hormone receptor status at diagnosis into a Cox proportional hazard model. Excluding mutations carriers, a horizontal family history (5% of all cases) was significantly associated with tubular tumor type [OR = 3.87(1.44-10.41)]. A vertical family history (23% of all cases) was significantly related to tumor multifocality [OR = 2.30(1.51-3.50)], tumor bilaterality [OR = 2.08(1.44-3.00)] and screening detection [OR = 1.50(1.10-2.05)]. No significant difference in survival could be seen between patients with none, horizontal or vertical family history. However, germline mutation carriers (BRCA1/2, TP53 or CDKN2A, present in 0.95% of the cases) had a significantly worse survival. Screening detected cases, HRT ever users and patients with estrogen receptor positive tumors had a significantly better survival adjusting for age at diagnosis, tumor size, lymph node status and presence of distant metastases at diagnosis. Factors associated with a horizontal family history were found, defining a possible phenotype for a recessive inheritance: tubular breast cancer.
authors.affiliation: Department of Oncology, Clinical Sciences, Lund University Hospital, Lund University, Barngatan 2b, 221 85 Lund, Sweden.
authors.forename: Carolina
authors.initials: C
authors.lastname: Ellberg
authors.forename: Göran
authors.initials: G
authors.lastname: Jönsson
authors.forename: Håkan
authors.initials: H
authors.lastname: Olsson
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics / Q000401:mortality / Q000628:therapy; D002288:Adenocarcinoma, Mucinous / Q000235:genetics / Q000401:mortality / Q000628:therapy; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D019313:BRCA1 Protein / Q000235:genetics; D024682:BRCA2 Protein / Q000235:genetics; D001943:Breast Neoplasms / Q000235:genetics* / Q000401:mortality* / Q000628:therapy; D018270:Carcinoma, Ductal, Breast / Q000235:genetics / Q000401:mortality / Q000628:therapy; D002285:Carcinoma, Intraductal, Noninfiltrating / Q000235:genetics / Q000401:mortality / Q000628:therapy; D018275:Carcinoma, Lobular / Q000235:genetics / Q000401:mortality / Q000628:therapy; D018276:Carcinoma, Medullary / Q000235:genetics / Q000401:mortality / Q000628:therapy; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000235:genetics; D004252:DNA Mutational Analysis; D004273:DNA, Neoplasm / Q000235:genetics; D005260:Female; D005808:Genes, Recessive; D020022:Genetic Predisposition to Disease; D005838:Genotype; D020249:Hormone Replacement Therapy; D006801:Humans; D008207:Lymphatic Metastasis; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D010641:Phenotype; D016133:Polymerase Chain Reaction; D011247:Pregnancy; D011379:Prognosis; D011960:Receptors, Estrogen / Q000378:metabolism; D011980:Receptors, Progesterone / Q000378:metabolism; D015996:Survival Rate; D016159:Tumor Suppressor Protein p53 / Q000235:genetics; D055815:Young Adult
chemical_list: D019313:BRCA1 Protein; D024682:BRCA2 Protein; D019941:Cyclin-Dependent Kinase Inhibitor p16; D004273:DNA, Neoplasm; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53