5 Family history suggestive of an inherited susceptibility to breast cancer and treatment outcome in...

Proceedings of the 39th Annual ASTRO Meeting 137

5 FAMILY HISTORY SUGGESTIVE OF AN INHERITED SUSCEPTIBILITY TO BREAST CANCER AND TREATMENT OUTCOME IN YOUNG WOMEN AmER BREAST-CONSERVING THERAPY

Chabner E,’ Nixon AJ,l Garber J,2 Gelman R,l Bornstein B,’ Connolly J,3 Hetelehidis S,’ Recht A,’ Schnitt S,3 Silver ~,l and Harris JR1

’ Joint Center for Radiation Therapy, * Dana-Farber Cancer Institute, 3 Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA

PURPOSE: To determine whether outcome after conservative surgery and radiation therapy for young women is affected by having a family history (FH) suggestive of an inherited susceptibility to breast cancer.

MATERIALS AND METHODS: Between 1968 and 1986,205 patients 36 years of age or younger at diagnosis were treated with breast-conserving surgery and radiation therapy for clinical stage I or II invasive breast cancer. Three patients were not evaluable for FH; the remainder constitute the study population. At the time of diagnosis, 34 patients (I 7%; 95% Cl 12.29%) had a mother or sister who had breast cancer diagnosed before age 50 years or who had ovarian cancer (2 cases) and were recorded as having a positive FH. This definition was chosen for clinical utility and to maximize the probability of inherited breast cancer within this sub-group (average 40-50%). Without genetic testing, the possibility of misclassification exists in both groups. The median age at diagnosis ofthe 34 patients with a positive FH was 33 years and was the same as the median age ofthe 168 patients in whom the FH was negative. All but 2 patients (99%) had a potential follow-up time of at least 5 years; 173 patients (86%) had a potential follow-up time of at least IO years.

RESULTS: Distributions of tumor size, pathologic nodal involvement, histologtc type. histologic grade, the presence of an extensive intraductal component or lymphatic vascular invasion, volume of tissue excised, and use of adjuvant chemotherapy did not differ significantly by FH. Table I shows the dwtribution of the sites of first failure within the first 5 years of follow-up. The overall pattern of failure was significantly different (p=O.O3) behveen patients with a positive FH and those with a negative FH; however, there was no statistically significant difference (Fisher Exact Test) in percentage of patients with no evidence ofdisease or local failure. At 5 years follow-up, the development ofan opposite breast cancer was significantly more common in women with a positive FH (12% vs 4% for opposite breast cancer only; 15% vs 5% for opposite breast cancer as a component of first failure, p=O.O09). At IO years follow-up, similar results were seen. Opposite breast cancer, as a first site of failure, was again more common in patients with a positive FH (24% vs 5% alone; 27% vs 7% as a component of first failure, p=O.O005). Patients with a positive FH had a significantly longer time to distant failure (p=O.O3, two-sided log rank test, Figure I). All of these comparisons were qualitatively similar in the sub-group of patients age 32 or younger and in the sub-group age 33-36.

FIGURE 1: Time to Distant Failure TABLE I: Distribution orsites of First Failure(bYear Crude Percentages)

Family No Evidence Local Failure Opposite History of Disease (+I- Other Failure) Breast Cancer

Only Positive 71% 9% 12% @=34)

Negative 57% 13% 4% (n=166)

Distant/Regional Failure or Death

From Other Causes 9%

26%

CONCLUSIONS: These results imply that young women with a family history suggestive of an inherited susceptibility to breast cancer do&have a higher risk of local failure following breast-conserving therapy, and have a b rate of dxtant failure than patients without such a history However, these patients appear to be at higher risk of developing an opposite breast cancer, and should be apprised of this risk at the time of diagnosis. We are now attempting to assess

outcome in relation to the results of genetic testing.

6 LOCAL RECURRENCES AND DISTANT METASTASES AFTER BREAST-CONSERVATIVE TREATMENTS IN A POPULATION AT VERY LOW RISK OF RECURRENCE ARE VERY DEPENDENT EVENTS.

Didier Cowen’, Jocelyne Jacquemie?. Grlles Houvenasghe13, Patnce Viens4, Dominrque Maraninchi4, Bardou’. Michel Resbeut’

Brigitte Puigs, Valerie-Jeanne

Departments of Radratton Oncology’, Pathology’, Surgery3, Chemotherapy4 and Statistics’, Paoli-Calmettes Cancer Center, Marserlle, France.

PURPOSE. Assessment of the relatrve ments of individual factors Influencing the risks of loco-regional failure (LRF) and metastases (M) after breast-preserving treatments IS made difficult by the marked inhomogeneities within the published series: short follow-up, use of chemotherapy, nodal status, margins of resection. We therefore selected a very homogenous population wrth an expected Iow- risk of recurrence to identify high-risk subgroups which may need more aggressive treatments.

MATERIALS AND METHODS’ Between 1980 and 1995, 3697 women wrth breast cancer were referred to Paolr-Calmettes Cancer Center, Marseille. Patients Included rn the study had undergone axillary dissection and were node negative (n=1840), were treated with conservative surgery (usually lumpectomy) and standard radiotherapy (n=1241), had histologrcal tumor sizes r: 50 mm, recaved no chemotherapy (n=1024), and had negative margins of resection (n=756). Hormonal therapy was given to 238 women (31 5%): castration for premenopausal women (n=92), tamoxrfen for postmenopausal women (n=146). The following factors were entered in the univariate analysis: age (I 40 yrs vs > 40 yrs.), menopausal status, hormonal treatment , peritumoral vessel invasron (PVI), histologic multifocalrty (HM), extensive intraductal component (EIC), estrogen receptor (ER) and progesterone receptor (PR) status, SBR grade (I vs II vs Ill) and histologrcal size (~20 mm vs >20 mm). Factors statistrcally significant (p<O 05) in the univariate analysis were entered in the Cox model.

RESULTS: Medran follow-up was 62 months (range 3-194). Median age was 55 yrs (range 27-85). Median tumor size was 15 mm (range 2-50). There were 76.4% ER+ and 72 1% PR+ tumors. PVI was found in 184 tumors and EIC only rn 30 tumors whereas HM was found in 106 cases There were 53 local recurrences, 8 locoregional failures and 65 metastases as frrst event, The yearly condrtronal event probabrlity for LRF and M was 1 8% and 1 6% respectively, constant over the years. Five and ten-year freedom from reccurence rates were 92.7% [90.4%-94 9%] and 81.6% [76 2%-86 9%] respectively for LRFs, and 91.6% [89.2%-94%] and 83.6% [79%-88.1%] respectrvely for M. Patients with HM (p=O.O016), PVI (p=O.O093), age 2 40yrs (p=O.O15), and grade Ill disease (p=O.O46) had more LRFs. In the multrvariate analysis HM (p=O.O076), PVI (p=O.O21) and age 2 40yrs (p=O 024) were independant prognostic factors of LRF Five and ten-year freedom from M was 67% and 44.6% respectrvely, for patients who had a local recurrence Patients with a tumor size >20 mm (p=O.O013), aged 2 40yrs (p=O.O019), and HM (p=O.O195), had more M. In the multrvariate analysis a tumor size >20 mm (p=O.O013), age 5 40 yrs (p=O.O03), and HM (p=O.O41) were rndependant prognostic factors of drstant failure

CONCLUSION In thus <( good prognoses ,> populatron, LRF and M shared similar prognostrc factors and had equal yearly probabrlrtres of occurence The frequency of M In patients who had a local recurrence showed a fourfold increase when compared with patients who had no such event We conclude that In this subset of patients local recurrence is evidence of tumor aggressiveness. We have identified a hrgh-risk subgroup whrch could benefit of a more aggressive inrtial treatment.