Abstract
BACKGROUND. The purpose of this investigation was to determine if there are pathobiologic differences between BRCA1-related and BRCA2-related hereditary breast cancer (HBC) and non-HBC. METHODS. On the basis of linkage to chromosomes 17q or 13q and/or the presence of ovarian and male breast cancer, HBC families were classified as either 'BRCA1-related' (26 families, 90 breast cancer pathology cases) or 'Other' (26 families, 85 cases), in which most BRCA2 cases were likely to reside. Cases were compared with 187 predominantly non-HBC cases. Tumors were assessed for histologic type, grade, and ploidy and S-phase fraction by quantitative DNA flow cytometry. Clinical presentation and available follow-up data were obtained. RESULTS. BRCA1- related and Other HBC patients each presented at lower stage (P = 0.003) and earlier age than non-HBC patients (mean, 42.8 years and 47.1 years vs. 62.9 years, P <0.0001). Compared with non-HBC, invasive BRCA1-related HBC had a lower diploidy rate (13% vs. 35%; P = 0.002), lower mean aneuploid DNA index (1.53 vs. 1.73; P = 0.002), and strikingly higher proliferation rates (mitotic grade 3; odds ratio [OR] = 4.42; P = 0.001; aneuploid mean S-phase fraction 16.5% vs. 9.3%, P <0.0001). Other HBC patients, including patients in two BRCA2-linked families, had more tubular-lobular group (TLG) carcinomas (OR = 2.56, P = 0.007). All trends were independent of age. A nonsignificant trend toward better crude survival in both HBC groups was age and stage- dependent. Compared with Other HBC, BRCA1-related HBC patients had fewer recurrences (P = 0.013), a trend toward lower specific death rates, and fared no worse than breast cancer patients at large. Other HBC patients, despite neutral prognostic indicators, fared worse. CONCLUSIONS. BRCA1-related HBCs are more frequently aneuploid and have higher tumor cell proliferation rates compared with Other HBC. Despite these adverse prognostic features, BRCA1- related HBC patients have paradoxically lower recurrence rates than Other HBC patients. The excess of TLG cancers in the 'Other' HBC group may be associated with BRCA2 linkage.
| Original language | English |
|---|---|
| Pages (from-to) | 697-709 |
| Number of pages | 13 |
| Journal | Cancer |
| Volume | 77 |
| Issue number | 4 |
| DOIs | |
| State | Published - Feb 15 1996 |
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All Science Journal Classification (ASJC) codes
- Cancer Research
- Oncology
Cite this
Hereditary breast cancer : Pathobiology, prognosis, and BRCA1 and BRCA2 gene linkage. / Marcus, Joseph N.; Watson, Patrice; Page, David L.; Narod, Steven A.; Lenoir, Gilbert M.; Tonin, Patricia; Linder-Stephenson, Lisa; Salerno, Giovanni; Conway, Theresa A.; Lynch, Henry T.
In: Cancer, Vol. 77, No. 4, 15.02.1996, p. 697-709.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Hereditary breast cancer
T2 - Pathobiology, prognosis, and BRCA1 and BRCA2 gene linkage
AU - Marcus, Joseph N.
AU - Watson, Patrice
AU - Page, David L.
AU - Narod, Steven A.
AU - Lenoir, Gilbert M.
AU - Tonin, Patricia
AU - Linder-Stephenson, Lisa
AU - Salerno, Giovanni
AU - Conway, Theresa A.
AU - Lynch, Henry T.
PY - 1996/2/15
Y1 - 1996/2/15
N2 - BACKGROUND. The purpose of this investigation was to determine if there are pathobiologic differences between BRCA1-related and BRCA2-related hereditary breast cancer (HBC) and non-HBC. METHODS. On the basis of linkage to chromosomes 17q or 13q and/or the presence of ovarian and male breast cancer, HBC families were classified as either 'BRCA1-related' (26 families, 90 breast cancer pathology cases) or 'Other' (26 families, 85 cases), in which most BRCA2 cases were likely to reside. Cases were compared with 187 predominantly non-HBC cases. Tumors were assessed for histologic type, grade, and ploidy and S-phase fraction by quantitative DNA flow cytometry. Clinical presentation and available follow-up data were obtained. RESULTS. BRCA1- related and Other HBC patients each presented at lower stage (P = 0.003) and earlier age than non-HBC patients (mean, 42.8 years and 47.1 years vs. 62.9 years, P <0.0001). Compared with non-HBC, invasive BRCA1-related HBC had a lower diploidy rate (13% vs. 35%; P = 0.002), lower mean aneuploid DNA index (1.53 vs. 1.73; P = 0.002), and strikingly higher proliferation rates (mitotic grade 3; odds ratio [OR] = 4.42; P = 0.001; aneuploid mean S-phase fraction 16.5% vs. 9.3%, P <0.0001). Other HBC patients, including patients in two BRCA2-linked families, had more tubular-lobular group (TLG) carcinomas (OR = 2.56, P = 0.007). All trends were independent of age. A nonsignificant trend toward better crude survival in both HBC groups was age and stage- dependent. Compared with Other HBC, BRCA1-related HBC patients had fewer recurrences (P = 0.013), a trend toward lower specific death rates, and fared no worse than breast cancer patients at large. Other HBC patients, despite neutral prognostic indicators, fared worse. CONCLUSIONS. BRCA1-related HBCs are more frequently aneuploid and have higher tumor cell proliferation rates compared with Other HBC. Despite these adverse prognostic features, BRCA1- related HBC patients have paradoxically lower recurrence rates than Other HBC patients. The excess of TLG cancers in the 'Other' HBC group may be associated with BRCA2 linkage.
AB - BACKGROUND. The purpose of this investigation was to determine if there are pathobiologic differences between BRCA1-related and BRCA2-related hereditary breast cancer (HBC) and non-HBC. METHODS. On the basis of linkage to chromosomes 17q or 13q and/or the presence of ovarian and male breast cancer, HBC families were classified as either 'BRCA1-related' (26 families, 90 breast cancer pathology cases) or 'Other' (26 families, 85 cases), in which most BRCA2 cases were likely to reside. Cases were compared with 187 predominantly non-HBC cases. Tumors were assessed for histologic type, grade, and ploidy and S-phase fraction by quantitative DNA flow cytometry. Clinical presentation and available follow-up data were obtained. RESULTS. BRCA1- related and Other HBC patients each presented at lower stage (P = 0.003) and earlier age than non-HBC patients (mean, 42.8 years and 47.1 years vs. 62.9 years, P <0.0001). Compared with non-HBC, invasive BRCA1-related HBC had a lower diploidy rate (13% vs. 35%; P = 0.002), lower mean aneuploid DNA index (1.53 vs. 1.73; P = 0.002), and strikingly higher proliferation rates (mitotic grade 3; odds ratio [OR] = 4.42; P = 0.001; aneuploid mean S-phase fraction 16.5% vs. 9.3%, P <0.0001). Other HBC patients, including patients in two BRCA2-linked families, had more tubular-lobular group (TLG) carcinomas (OR = 2.56, P = 0.007). All trends were independent of age. A nonsignificant trend toward better crude survival in both HBC groups was age and stage- dependent. Compared with Other HBC, BRCA1-related HBC patients had fewer recurrences (P = 0.013), a trend toward lower specific death rates, and fared no worse than breast cancer patients at large. Other HBC patients, despite neutral prognostic indicators, fared worse. CONCLUSIONS. BRCA1-related HBCs are more frequently aneuploid and have higher tumor cell proliferation rates compared with Other HBC. Despite these adverse prognostic features, BRCA1- related HBC patients have paradoxically lower recurrence rates than Other HBC patients. The excess of TLG cancers in the 'Other' HBC group may be associated with BRCA2 linkage.
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UR - http://www.scopus.com/inward/citedby.url?scp=13344262707&partnerID=8YFLogxK
U2 - 10.1002/(SICI)1097-0142(19960215)77:4<697::AID-CNCR16>3.0.CO;2-W
DO - 10.1002/(SICI)1097-0142(19960215)77:4<697::AID-CNCR16>3.0.CO;2-W
M3 - Article
C2 - 8616762
AN - SCOPUS:13344262707
VL - 77
SP - 697
EP - 709
JO - Cancer
JF - Cancer
SN - 0008-543X
IS - 4
ER -