Relationship Between Tumor Location and Relapse in 6,781 Women With Early Invasive Breast Cancer

Lohrisch, Caroline; Jackson, Jeremy S. H.; Jones, Amanda; Mates, Donna; Olivotto, Ivo A.

doi:10.1200/jco.2000.18.15.2828

Cited by 117 publications

(74 citation statements)

References 30 publications

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“…The median follow-up time and age at diagnosis for this cohort was 12.4 and 60 years, respectively. All patients had been referred to the British Columbia Cancer Agency and had staging, pathology, treatment, and follow-up information maintained by the BCOU (21,22). During the study era, f75% of all breast cancer cases in British Columbia were referred to the British Columbia Cancer Agency.…”

Section: Methodsmentioning

confidence: 99%

“…During the study era, f75% of all breast cancer cases in British Columbia were referred to the British Columbia Cancer Agency. Nonreferred patients were generally elderly or treated by mastectomy without indications for adjuvant therapy (21). The benign epithelial breast tissue array was composed of 120 samples obtained from patients without a diagnosis of breast cancer (Supplementary Table S1).…”

Section: Methodsmentioning

confidence: 99%

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Insulin-Like Growth Factor Binding Protein-2 Is a Novel Therapeutic Target Associated with Breast Cancer

Levitt

Eigl

et al. 2008

Clinical Cancer Research

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Purpose: Insulin-like growth factor (IGF) binding proteins (IGFBP) modulate interactions of IGF ligands with the IGF-I receptor. The role of IGFBPs, and specifically IGFBP-2, in breast cancer progression has been poorly defined. This study assesses the effect of IGFBP-2 on the behavior of human breast cancer using clinical specimens as well as in vitro and in vivo experimental systems. Experimental Design: 4,181 primary invasive breast cancers and 120 benign breast tissue samples were identified for tumor tissue microarray construction and immunostained with IGFBP-2 antibody. Estrogen receptor-negative MDA-MB-231cells constitutively overexpressing IGFBP-2 (MDA-MB-231BP-2) were created to assess the effect of IGFBP-2 gain-of-function. MDA-MB-468 cells, naturally expressing IGFBP-2, were used to determine the effect of IGFBP-2 loss-of-function using OGX-225, an antisense oligonucleotide drug candidate. Results: IGFBP-2 expression was significantly higher in breast cancer tissue compared with benign breast tissue. MDA-MB-231BP-2 cells grew more rapidly and were more resistant to paclitaxel both in vitro and in vivo compared with parental cells. OGX-225 decreased IGFBP-2 expression and attenuated the associated aggressive phenotype of MDA-MB-231BP-2 cells both in vitro and in vivo. Furthermore, OGX-225 inhibited the in vitro and in vivo growth of MDA-MB-468 cells. Conclusions: This study provides evidence that IGFBP-2 expression is associated with breast cancer. Novel therapeutics targeting IGFBP-2, such as OGX-225, merit further evaluation.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Insulin-Like Growth Factor Binding Protein-2 Is a Novel Therapeutic Target Associated with Breast Cancer

Levitt

Eigl

et al. 2008

Clinical Cancer Research

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“…There is growing evidence that tumors occurring in the inner quadrants have a higher breast cancer mortality. [9][10][11][12] However, the real impact of tumor location on the risk of IMC node metastases and on prognosis is still controversial, mainly because of the inconclusive findings in older studies. 4,[13][14][15] We used data from the Geneva Cancer Registry to evaluate the impact of tumor location on breast cancer mortality among women with stage I disease.…”

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confidence: 99%

Tumor Location of the Lower-Inner Quadrant Is Associated with an Impaired Survival for Women With Early-Stage Breast Cancer

et al. 2006

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Background: There is growing evidence that tumors of the inner quadrants (especially the lower-inner quadrant) metastasize more often to the internal mammary chain (IMC). As these metastases are not investigated, patients with lower-inner quadrant tumors have an increased risk of being under-staged and under-treated and may therefore have a higher risk of death from breast cancer.Methods: We identified all 1522 women operated for stage I breast cancer between 1984 and 2002 recorded at the population-based Geneva Cancer Registry. We compared breast cancer mortality risk by tumor location with multivariate Cox regression analysis that accounted for all factors linked to tumor location and survival.Results: Ten-year disease-specific survival was 93% (95%CI: 91-94%). Patients with breast cancer of the lower-inner quadrant (n = 118; 7.8%) had an importantly increased risk of dying of breast cancer compared to women with breast cancer of the upper-outer quadrant (multiadjusted Hazard Ratio: 2.3, 95%CI: 1.1-4.5, P = 0.0206). The over-mortality associated with this quadrant was particularly evident for tumors >10 mm (multiadjusted HR: 3.6, 95%CI: 1.6-7.9, P = 0.0016). There was no increased breast cancer mortality risk for tumors located in other quadrants.Conclusions: Tumor location in the lower-inner quadrant is an independent and important prognostic factor of stage I breast cancer. Further research is needed to evaluate if the overmortality of patients with stage I cancer of the lower-inner quadrant is indeed a result of under-treatment due to undetected IMC metastases. If so, patients with stage I breast cancer of the lower-inner quadrant are good candidates for systematic IMC investigation.

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“…The study reports also a fourfold reduction in internal mammary (IM) recurrence rate but the numbers are small. In fact, it is precisely the unidentified/untreated metastatic drainage to the IM nodes that is usually blamed for the worse prognosis associated with medial tumors compared to otherwise similar lateral ones [5]. Unfortunately, regional nodal irradiation was also associated with an increased risk of pulmonary fibrosis, cardiac fibrosis, and cardiac disease.…”

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confidence: 99%

A tailored approach to regional nodal irradiation

Avisar

2015

Breast Cancer Res Treat

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Regional nodal irradiation for breast cancer has recently been shown to improve disease-free survival, distant disease-free survival, and breast-related mortality but is associated with morbidity. A tailored approach adding regional nodal irradiation only to patients with involvement of the internal mammary nodes is improving prognosis while minimizing morbidity.The results of the EORTC trial on Internal Mammary and Medial Supraclavicular Irradiation in Breast Cancer were recently reported in NEJM (July 23 issue) [1]. Patients with centrally or medially located primary tumors irrespective of axillary involvement or externally located tumors with axillary involvement were randomized in a 1:1 fashion to the addition of regional nodal irradiation to the standard breast or chest wall radiation. The rationale behind the study was a reported 4-9 % involvement of the internal mammary nodes in patients with axillary node-negative breast cancer and 16-65 % in those with axillary nodepositive breast cancer [2][3][4]. The results demonstrate a small but significant benefit in disease-free survival, distant disease-free survival, and breast-related mortality. The study reports also a fourfold reduction in internal mammary (IM) recurrence rate but the numbers are small. In fact, it is precisely the unidentified/untreated metastatic drainage to the IM nodes that is usually blamed for the worse prognosis associated with medial tumors compared to otherwise similar lateral ones [5]. Unfortunately, regional nodal irradiation was also associated with an increased risk of pulmonary fibrosis, cardiac fibrosis, and cardiac disease. This associated morbidity might have contributed to the only marginal effect of regional irradiation on overall survival.The quoted rates of metastatic involvement of the IM nodes in the paper do not take into account the lymphatic drainage pattern from the primary tumor as easily mapped by lymphoscintigraphy. Drainage to the IM nodal chain is associated with an 8-27 % metastatic rate [6]. This subgroup of patients with metastatic IM nodes is the most likely to benefit from IM radiation. We routinely perform IM sentinel node biopsies for patients with lymphatic drainage to the IM chain, thereby selecting the specific subgroup for which additional IM radiation should be added and minimizing the morbidity associated with it. We have demonstrated [7] that this tailored approach to the IM chain can reverse the worse prognosis associated with lymphatic drainage to those nodes [8].

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Relationship Between Tumor Location and Relapse in 6,781 Women With Early Invasive Breast Cancer

Cited by 117 publications

References 30 publications

Insulin-Like Growth Factor Binding Protein-2 Is a Novel Therapeutic Target Associated with Breast Cancer

Insulin-Like Growth Factor Binding Protein-2 Is a Novel Therapeutic Target Associated with Breast Cancer

Tumor Location of the Lower-Inner Quadrant Is Associated with an Impaired Survival for Women With Early-Stage Breast Cancer

A tailored approach to regional nodal irradiation

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