Intact female Beagles from life-span studies in the Lovelace Respiratory Re
search Institute colony were examined for mammary tumor incidence. The bree
ding colony, founded in 1963, produced five generations from 28 founder fem
ales. After proportional hazards analysis, two maternal families were shown
to have markedly different phenotypes, one susceptible and one resistant t
o mammary neoplasia, as compared with the entire colony. When tumors were s
ubdivided into benign and malignant based on local invasiveness, familial d
ifferences in tumor incidence were preserved for each tumor type. Fifty-sev
en females in the susceptible family developed 149 benign and 39 malignant
tumors, and 95 females in the resistant family developed 70 benign and 20 m
alignant tumors. The ratio of benign to malignant tumors of about 4:1 for b
oth families was higher than expected. Using Kaplan-Meier and log-rank anal
yses, the susceptible family had a 50% malignant tumor incidence by age 13.
6 years, whereas the resistant family did not have a 50% incidence until 17
.0 years (P = 0.0065). Because of marked censoring, Kaplan-Meier analyses c
ould not provide an estimate of the 50% benign turner incidence; mean incid
ence age was calculated instead. These estimates for benign tumors for susc
eptible and resistant families were 10.8 and 13.8 years (P = 0.0001), respe
ctively. Using chi(2) tests, families had no differences in the occurrence
of the types of benign (P = 0.098) or malignant (P = 0.194) tumors or in th
e ratio of benign to malignant tumors (P = 0.778). Immunohistochemical anal
ysis of malignant tumors from both families did not demonstrate differences
in p53 mutation rate or p185(erbB-2) expression. These results suggest tha
t 1) genetic factors produce familial differences in the age of onset of bo
th benign and malignant mammary tumors; histologic types do not segregate b
y family; 2) the ratio of benign to malignant tumors is greater than former
ly reported; and 3) neither p53 nor p185(erbB-2) alterations are the basis
for the familial predisposition.