6 Local recurrences and distant metastases after breast-conservative treatments in a population at very low risk of recurrence are very dependent events

137

Proceedings of the 39th Annual ASTRO Meeting 5 FAMILY WOMEN

HISTORY SUGGESTIVE OF AN INHERITED AmER BREAST-CONSERVING THERAPY

Chabner

E,’

’ Joint Center PURPOSE: suggestive

Nixon

AJ,l

Garber

for Radiation

J,2 Gelman

Therapy,

R,l

Bornstein

* Dana-Farber

Cancer

To determine whether outcome after conservative of an inherited susceptibility to breast cancer.

SUSCEPTIBILITY

B,’

Connolly

Institute, surgery

T O BREAST

J,3 Hetelehidis

3 Beth Israel Deaconess and radiation

therapy

S,’

CANCER

AND

Recht A,’

Schnitt

Medical

Center,

for young

women

TREATMENT

S,3 Silver

Harvard

~,l and Harris

Medical

is affected

OUTCOME

School,

by having

IN YOUNG

JR1

Boston,

a family

MA

history

(FH)

Between 1968 and 1986,205 patients 36 years of age or younger at diagnosis were treated with breast-conserving surgery MATERIALS AND METHODS: 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) Local Failure Opposite Distant/Regional Family No Evidence Breast Cancer Failure or Death History of Disease (+I- Other Failure) Only From Other Causes 71% 9% 12% 9% Positive @=34) 57% 13% 4% 26% Negative (n=166) CONCLUSIONS: These results imply that young women with a family history suggestive of an inherited susceptibility to breast cancer do&have a higher However, these patients risk of local failure following breast-conserving therapy, and have a b rate of dxtant failure than patients without such a history We are now attempting to assess appear to be at higher risk of developing an opposite breast cancer, and should be apprised of this risk at the time of diagnosis. outcome in relation to the results of genetic testing.

6 LOCAL VERY

RECURRENCES AND DISTANT METASTASES AFTER LOW RISK OF RECURRENCE ARE VERY DEPENDENT

Didier Cowen’, Jocelyne Bardou’. Michel Resbeut’ Departments of Radratton Marserlle, France.

Jacquemie?.

PURPOSE. Assessment of (M) after breast-preserving use of chemotherapy, nodal risk of recurrence to identify

Oncology’,

Grlles

Houvenasghe13,

Pathology’,

Surgery3,

BREAST-CONSERVATIVE EVENTS. Patnce

Viens4,

Dominrque

Chemotherapy4

and

TREATMENTS

Maraninchi4, Statistics’,

IN A POPULATION

Brigitte

Puigs,

Paoli-Calmettes

AT

Valerie-Jeanne Cancer

Center,

the relatrve ments of individual factors Influencing the risks of loco-regional failure treatments IS made difficult by the marked inhomogeneities within the published status, margins of resection. We therefore selected a very homogenous population high-risk subgroups which may need more aggressive treatments.

(LRF) and metastases series: short follow-up, wrth an expected Iow-

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

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 of occurence The frequency of M In patients who had a local recurrence showed a fourfold increase when compared who had no such event We conclude that In this subset of patients local recurrence is evidence of tumor aggressiveness. identified a hrgh-risk subgroup whrch could benefit of a more aggressive inrtial treatment.

probabrlrtres with patients We have