Prognostic factors affecting the natural history of node-negative breast cancer

Trudeau, Maureen; Pritchard, Kathleen I.; Chapman, Judy‐Anne W.; Hanna, Wedad; Kahn, Harriette J.; Murray, David; Sawka, Carol; Mobbs, B.G.; Andrulis, Irene L.; McCready, David R.; Lickley, H. Lavina A.

doi:10.1007/s10549-004-1368-y

Cited by 43 publications

(26 citation statements)

References 50 publications

(59 reference statements)

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“…Online website permits clinicians the opportunity to explore trade-offs in risk-benefits for different patient management options for different ages, taking into account the severity of presenting disease, and differing co-morbidity states [4] . Concurrently, experience was reported from a smaller prospectively accrued single institution phase Ⅳ cohort at Women's College Hospital, where routine annual mammography starting at age 35 was employed in the 1960' s, following early scientific reports of its effectiveness [7,8] . This experience was from an era before both routine adjuvant radiotherapy and systemic therapy, and illustrated the effects of early detection [7,8] .…”

Section: Introductionmentioning

confidence: 99%

“…Concurrently, experience was reported from a smaller prospectively accrued single institution phase Ⅳ cohort at Women's College Hospital, where routine annual mammography starting at age 35 was employed in the 1960' s, following early scientific reports of its effectiveness [7,8] . This experience was from an era before both routine adjuvant radiotherapy and systemic therapy, and illustrated the effects of early detection [7,8] . At a median 8.2 years follow-up, 20% of those older than 65% and 3% of those under 65 died of other causes (P < 0.001).…”

Section: Introductionmentioning

confidence: 99%

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Competing risks of death in younger and older postmenopausal breast cancer patients

Chapman

Pritchard

Goss

et al. 2014

WJCO

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AIM:To show a new paradigm of simultaneously testing whether breast cancer therapies impact other causes of death. METHODS:MA.14 allocated 667 postmenopausal women to 5 years of tamoxifen 20 mg/daily ± 2 years of octreotide 90 mg, given by depot intramuscular injections monthly. Event-free survival was the primary endpoint of MA.14; at median 7.9 years, the tamoxifen+octreotide and tamoxifen arms had similar event-free survival (P = 0.62). Overall survival was a secondary endpoint, and the two trial arms also had similar overall survival (P = 0.86). We used the median 9.8 years follow-up to examine by intention-to-treat, the multivariate time-to-breast cancer-specific (BrCa) and other cause (OC) mortality with log-normal survival analysis adjusted by treatment and stratification factors. We tested whether baseline factors including Insulin-like growth factor 1 (IGF1), IGF binding protein-3, C-peptide, body mass index, and 25-OH vitamin D were associated with (1) all cause mortality, and if so; and (2) cause-specific mortality. We also fit step-wise forward cause-specific adjusted models. RESULTS:The analyses were performed on 329 patients allocated tamoxifen and 329 allocated tamoxifen+octreotide. The median age of MA.14 patients was 60.1 years: 447 (82%) < 70 years and 120 (18%) ≥ 70 years. There were 170 deaths: 106 (62.3%) BrCa; 55 (32.4%) OC, of which 24 were other malignancies, 31 other causes of death; 9 (5.3%) patients with unknown cause of death were excluded from competing risk assessments. BrCa and OC deaths were not significantly different by treatment arm (P = 0.40): tamoxifen patients experienced 50 BrCa and 32 OC deaths, while tamoxifen + octreotide patients experienced 56 BrCa and 23 OC deaths. Proportionately more deaths (P = 0.004) were from BrCa for patients RETROSPECTIVE STUDYCompeting risks of death in younger and older postmenopausal breast cancer patients < 70 years, where 70% of deaths were due to BrCa, compared to 54% for those ≥ 70 years of age. The proportion of deaths from OC increased with increasing body mass index (BMI) (P = 0.02). Higher pathologic T and N were associated with more BrCa deaths (P < 0.0001 and 0.002, respectively). The cumulative hazard plot for BrCa and OC mortality indicated the concurrent accrual of both types of death throughout followup, that is the existence of competing risks of mortality. MA.14 therapy did not impact mortality (P = 0.77). Three baseline patient and tumor characteristics were differentially associated with cause of death: older patients experienced more OC (P = 0.01) mortality; patients with T1 tumors and hormone receptor positive tumors had less BrCa mortality (respectively, P = 0.01, P = 0.06). Additionally, step-wise cause-specific models indicated that patients with node negative disease experienced less BrCa mortality (P = 0.002); there was weak evidence that, lower C-peptide (P = 0.08) was associated with less BrCa mortality, while higher BMI (P = 0.01) was associated with worse OC mortality. CONCLUSION:We demonstrate here a ne...

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Competing risks of death in younger and older postmenopausal breast cancer patients

Chapman

Pritchard

Goss

et al. 2014

WJCO

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“…1 High tumor grade is associated with decreased overall survival, 2 but it also predicts increased response to neoadjuvant chemotherapy. 3 Lack of sufficient reproducibility and objectivity limit the clinical utility of histologic grade as a prognostic or predictive factor.…”

Section: Introductionmentioning

confidence: 99%

Genomic Grade Index Is Associated With Response to Chemotherapy in Patients With Breast Cancer

Liedtke

Hatzis

Symmans

et al. 2009

JCO

171

110

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A B S T R A C T PurposeThe genomic grade index (GGI) is a 97-gene measure of histological tumor grade. High GGI is associated with decreased relapse-free survival in patients receiving either endocrine or no systemic adjuvant therapy. Herein we examined whether GGI predicts pathologic response to neoadjuvant chemotherapy in patients with HER-2-normal breast cancer. MethodsGene expression data (gene chips) was generated from fine-needle aspiration biopsies (n ϭ 229) prospectively collected before neoadjuvant paclitaxel, fluorouracil, doxorubicin, and cyclophosphamide chemotherapy. Pathologic response was quantified using the residual cancer burden (RCB) method. The association between the GGI and pathologic response was assessed in univariate and multivariate analyses. The performance of a response predictor combining clinical variables and GGI was evaluated under cross-validation. ResultsEighty-five percent of grade 1 tumors had low GGI, 89% of grade 3 tumors had high GGI, and 63% of grade 2 tumors had low GGI. Among both estrogen receptor (ER)-positive and -negative cancers, high GGI score was associated with pathologic complete response (RCB-0) or minimal residual disease (RCB-1). A multivariate model combining GGI and clinical parameters had an overall accuracy of 71%, compared with 58% for the GGI alone, for prediction of pathologic response. However, high GGI score was also associated with significantly worse distant relapse-free survival in patients with ER-positive cancer (P ϭ .005), and was not associated with survival in patients with ER-negative cancer. ConclusionHigh GGI is associated with increased sensitivity to neoadjuvant paclitaxel plus fluorouracil, adriamycin, and cyclophosphamide chemotherapy in both ER-negative and ER-positive patients, but it remains a predictor of worse survival in ER-positive patients.

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“…Each slice was put in as many separate cassettes as necessary and paraffin embedded. The median of blocks per patients was 3 (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17). In total, 3 blocks per tumor were obtained in 68 cases (72%) and 4-17 blocks in 14 cases.…”

Section: Tissue Samples and Histological Examinationmentioning

confidence: 99%

“…[4][5][6][7] In routine practice, the identification of lymphovascular invasion is subject to interobserver variability. Nevertheless, definite peritumoral lymphovascular invasion in the breast surrounding invasive carcinoma, without distinguishing blood vessels and lymphatics, was found with the same incidence by two teams in 19% of 1320 and 2760 node-negative patients, respectively.…”

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confidence: 99%

D2-40 in breast cancer: should we detect more vascular emboli?

et al. 2009

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Peritumoral emboli assessed on hematoxylin-eosin-stained slides are taken into account for treatment of patients with operable breast cancer. We assessed whether immunostaining with D2-40 improves the prognostic significance of emboli in a group of tumors with a large immunohistochemical sampling and a longterm follow-up. Topography, number, and extension of hematoxylin-eosin and D2-40 emboli were compared in 94 node-negative breast cancers (median number of immunostained slides per tumor: 3). Metastatasis-free survival of patients with or without hematoxylin-eosin and/or D2-40 emboli were evaluated (median follow-up of 178 months). Hematoxylin-eosin emboli were detected in 14 (15%) tumors and were located at distance from the tumor. D2-40 emboli were detected in 39 (41%) tumors and was often multiple (n ¼ 30), extensive (n ¼ 23), located within (n ¼ 13), close to (n ¼ 10) or at distance from the tumor (n ¼ 16). The 12 distant hematoxylin-eosin and D2-40 emboli were located in the same vessels (seven missed at the first hematoxylin-eosin examination and secondarily diagnosed by D2-40 staining). A difference in metastasis-free survival was found only between patients with no D2-40 emboli and those with distant D2-40 emboli (P ¼ 0.02). D2-40 emboli located within or close to the tumor had no prognostic value. Comparing the metastasis-free survival of patients with or without hematoxylin-eosin emboli, the prognostically unfavorable significance of hematoxylin-eosin emboli was improved when taking into account the seven patients with missed emboli at the first examination and secondarily diagnosed by D2-40 staining (P ¼ 0.006 vs 0.003). To conclude, D2-40 increases the diagnostic sensitivity of emboli in breast carcinoma and the high incidence of D2-40 emboli might be related to the number of immunostained slides per case. Nevertheless, only distant D2-40 þ emboli had a prognostic impact. In practice, D2-40 might be useful to detect missed hematoxylin-eosin emboli especially in cases without any other prognostically unfavorable criterion.

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Prognostic factors affecting the natural history of node-negative breast cancer

Cited by 43 publications

References 50 publications

Competing risks of death in younger and older postmenopausal breast cancer patients

Competing risks of death in younger and older postmenopausal breast cancer patients

Genomic Grade Index Is Associated With Response to Chemotherapy in Patients With Breast Cancer

D2-40 in breast cancer: should we detect more vascular emboli?

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