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Annexin A1 expression in a pooled breast cancer series: association with tumor subtypes and prognosis.

Sobral-Leite M, Wesseling J, Smit VT, Nevanlinna H, van Miltenburg MH, Sanders J, Hofland I, Blows FM, Coulson P, Patrycja G, Schellens JH, Fagerholm R, Heikkilä P, Aittomäki K, Blomqvist C, Provenzano E, Ali HR, Figueroa J, Sherman M, Lissowska J, Mannermaa A, Kataja V, Kosma VM, Hartikainen JM, Phillips KA, kConFab/AOCS InvestigatorsCouch FJ, Olson JE, Vachon C, Visscher D, Brenner H, Butterbach K, Arndt V, Holleczek B, Hooning MJ, Hollestelle A, Martens JW, van Deurzen CH, van de Water B, Broeks A, Chang-Claude J, Chenevix-Trench G, Easton DF, Pharoah PD, García-Closas M, de Graauw M, Schmidt MK - BMC Med (2015)

Bottom Line: ANXA1 was also highly expressed in BCAC tumors that were poorly differentiated, triple negative, EGFR-CK5/6 positive or had developed in patients at a young age.ANXA1 was a significant independent predictor of survival in HER2+ patients (10-years BCSS: HRadj = 1.70; 95 % CI = 1.17-2.45).ANXA1 is overexpressed in familial breast cancer patients with BRCA1/2 mutations and correlated with poor prognosis features: triple negative and poorly differentiated tumors.

View Article: PubMed Central - PubMed

Affiliation: Division of Molecular Pathology, Netherlands Cancer Institute, Amsterdam, The Netherlands. m.leite@nki.nl.

ABSTRACT

Background: Annexin A1 (ANXA1) is a protein related with the carcinogenesis process and metastasis formation in many tumors. However, little is known about the prognostic value of ANXA1 in breast cancer. The purpose of this study is to evaluate the association between ANXA1 expression, BRCA1/2 germline carriership, specific tumor subtypes and survival in breast cancer patients.

Methods: Clinical-pathological information and follow-up data were collected from nine breast cancer studies from the Breast Cancer Association Consortium (BCAC) (n = 5,752) and from one study of familial breast cancer patients with BRCA1/2 mutations (n = 107). ANXA1 expression was scored based on the percentage of immunohistochemical staining in tumor cells. Survival analyses were performed using a multivariable Cox model.

Results: The frequency of ANXA1 positive tumors was higher in familial breast cancer patients with BRCA1/2 mutations than in BCAC patients, with 48.6 % versus 12.4 %, respectively; P <0.0001. ANXA1 was also highly expressed in BCAC tumors that were poorly differentiated, triple negative, EGFR-CK5/6 positive or had developed in patients at a young age. In the first 5 years of follow-up, patients with ANXA1 positive tumors had a worse breast cancer-specific survival (BCSS) than ANXA1 negative (HRadj = 1.35; 95 % CI = 1.05-1.73), but the association weakened after 10 years (HRadj = 1.13; 95 % CI = 0.91-1.40). ANXA1 was a significant independent predictor of survival in HER2+ patients (10-years BCSS: HRadj = 1.70; 95 % CI = 1.17-2.45).

Conclusions: ANXA1 is overexpressed in familial breast cancer patients with BRCA1/2 mutations and correlated with poor prognosis features: triple negative and poorly differentiated tumors. ANXA1 might be a biomarker candidate for breast cancer survival prediction in high risk groups such as HER2+ cases.

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Adjuvant treatment response. Survival curves, crude hazard ratios (HR) and adjusted hazard ratios (HRadj) according to ANXA1 expression in patients from BCAC with high risk of recurrence (HER2+ and/or pN+) who received anthracycline-based adjuvant chemotherapy. Overall survival and disease-free survival in (a, b) patients under 50 years old and (c, d) patients over 49 and under 70 years old. Hazard ratios were adjusted for: age of diagnosis; tumor grade; tumor size; lymph node metastasis; ER/PR status; and HER2 status. Note: low risk of recurrence was defined as: 35 years old or older; lymph node negative; tumor size ≥2 cm with any grade or tumor size ≥1 cm with tumor grade ≥2; high risk of recurrence was defined as: HER2+ and/or lymph node positive. ANXA1: Annexin A1; BCAC: Breast Cancer Association Consortium; HR: Hazard ratio
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Fig3: Adjuvant treatment response. Survival curves, crude hazard ratios (HR) and adjusted hazard ratios (HRadj) according to ANXA1 expression in patients from BCAC with high risk of recurrence (HER2+ and/or pN+) who received anthracycline-based adjuvant chemotherapy. Overall survival and disease-free survival in (a, b) patients under 50 years old and (c, d) patients over 49 and under 70 years old. Hazard ratios were adjusted for: age of diagnosis; tumor grade; tumor size; lymph node metastasis; ER/PR status; and HER2 status. Note: low risk of recurrence was defined as: 35 years old or older; lymph node negative; tumor size ≥2 cm with any grade or tumor size ≥1 cm with tumor grade ≥2; high risk of recurrence was defined as: HER2+ and/or lymph node positive. ANXA1: Annexin A1; BCAC: Breast Cancer Association Consortium; HR: Hazard ratio

Mentions: Part of these patients (24.2 %) received anthracycline-based adjuvant chemotherapy. In the same high risk group aged 50–69 years, the ANXA1 positive cases presented a suggestive worse outcome after anthracycline-based adjuvant chemotherapy (10-years OS: HRadj = 2.48; 95 % CI = 0.82–7.50; Fig. 3 and BCSS: HRadj = 2.96; 95 % CI = 0.92–9.57; Additional file 7: Figure S4F).Fig. 3


Annexin A1 expression in a pooled breast cancer series: association with tumor subtypes and prognosis.

Sobral-Leite M, Wesseling J, Smit VT, Nevanlinna H, van Miltenburg MH, Sanders J, Hofland I, Blows FM, Coulson P, Patrycja G, Schellens JH, Fagerholm R, Heikkilä P, Aittomäki K, Blomqvist C, Provenzano E, Ali HR, Figueroa J, Sherman M, Lissowska J, Mannermaa A, Kataja V, Kosma VM, Hartikainen JM, Phillips KA, kConFab/AOCS InvestigatorsCouch FJ, Olson JE, Vachon C, Visscher D, Brenner H, Butterbach K, Arndt V, Holleczek B, Hooning MJ, Hollestelle A, Martens JW, van Deurzen CH, van de Water B, Broeks A, Chang-Claude J, Chenevix-Trench G, Easton DF, Pharoah PD, García-Closas M, de Graauw M, Schmidt MK - BMC Med (2015)

Adjuvant treatment response. Survival curves, crude hazard ratios (HR) and adjusted hazard ratios (HRadj) according to ANXA1 expression in patients from BCAC with high risk of recurrence (HER2+ and/or pN+) who received anthracycline-based adjuvant chemotherapy. Overall survival and disease-free survival in (a, b) patients under 50 years old and (c, d) patients over 49 and under 70 years old. Hazard ratios were adjusted for: age of diagnosis; tumor grade; tumor size; lymph node metastasis; ER/PR status; and HER2 status. Note: low risk of recurrence was defined as: 35 years old or older; lymph node negative; tumor size ≥2 cm with any grade or tumor size ≥1 cm with tumor grade ≥2; high risk of recurrence was defined as: HER2+ and/or lymph node positive. ANXA1: Annexin A1; BCAC: Breast Cancer Association Consortium; HR: Hazard ratio
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4489114&req=5

Fig3: Adjuvant treatment response. Survival curves, crude hazard ratios (HR) and adjusted hazard ratios (HRadj) according to ANXA1 expression in patients from BCAC with high risk of recurrence (HER2+ and/or pN+) who received anthracycline-based adjuvant chemotherapy. Overall survival and disease-free survival in (a, b) patients under 50 years old and (c, d) patients over 49 and under 70 years old. Hazard ratios were adjusted for: age of diagnosis; tumor grade; tumor size; lymph node metastasis; ER/PR status; and HER2 status. Note: low risk of recurrence was defined as: 35 years old or older; lymph node negative; tumor size ≥2 cm with any grade or tumor size ≥1 cm with tumor grade ≥2; high risk of recurrence was defined as: HER2+ and/or lymph node positive. ANXA1: Annexin A1; BCAC: Breast Cancer Association Consortium; HR: Hazard ratio
Mentions: Part of these patients (24.2 %) received anthracycline-based adjuvant chemotherapy. In the same high risk group aged 50–69 years, the ANXA1 positive cases presented a suggestive worse outcome after anthracycline-based adjuvant chemotherapy (10-years OS: HRadj = 2.48; 95 % CI = 0.82–7.50; Fig. 3 and BCSS: HRadj = 2.96; 95 % CI = 0.92–9.57; Additional file 7: Figure S4F).Fig. 3

Bottom Line: ANXA1 was also highly expressed in BCAC tumors that were poorly differentiated, triple negative, EGFR-CK5/6 positive or had developed in patients at a young age.ANXA1 was a significant independent predictor of survival in HER2+ patients (10-years BCSS: HRadj = 1.70; 95 % CI = 1.17-2.45).ANXA1 is overexpressed in familial breast cancer patients with BRCA1/2 mutations and correlated with poor prognosis features: triple negative and poorly differentiated tumors.

View Article: PubMed Central - PubMed

Affiliation: Division of Molecular Pathology, Netherlands Cancer Institute, Amsterdam, The Netherlands. m.leite@nki.nl.

ABSTRACT

Background: Annexin A1 (ANXA1) is a protein related with the carcinogenesis process and metastasis formation in many tumors. However, little is known about the prognostic value of ANXA1 in breast cancer. The purpose of this study is to evaluate the association between ANXA1 expression, BRCA1/2 germline carriership, specific tumor subtypes and survival in breast cancer patients.

Methods: Clinical-pathological information and follow-up data were collected from nine breast cancer studies from the Breast Cancer Association Consortium (BCAC) (n = 5,752) and from one study of familial breast cancer patients with BRCA1/2 mutations (n = 107). ANXA1 expression was scored based on the percentage of immunohistochemical staining in tumor cells. Survival analyses were performed using a multivariable Cox model.

Results: The frequency of ANXA1 positive tumors was higher in familial breast cancer patients with BRCA1/2 mutations than in BCAC patients, with 48.6 % versus 12.4 %, respectively; P <0.0001. ANXA1 was also highly expressed in BCAC tumors that were poorly differentiated, triple negative, EGFR-CK5/6 positive or had developed in patients at a young age. In the first 5 years of follow-up, patients with ANXA1 positive tumors had a worse breast cancer-specific survival (BCSS) than ANXA1 negative (HRadj = 1.35; 95 % CI = 1.05-1.73), but the association weakened after 10 years (HRadj = 1.13; 95 % CI = 0.91-1.40). ANXA1 was a significant independent predictor of survival in HER2+ patients (10-years BCSS: HRadj = 1.70; 95 % CI = 1.17-2.45).

Conclusions: ANXA1 is overexpressed in familial breast cancer patients with BRCA1/2 mutations and correlated with poor prognosis features: triple negative and poorly differentiated tumors. ANXA1 might be a biomarker candidate for breast cancer survival prediction in high risk groups such as HER2+ cases.

Show MeSH
Related in: MedlinePlus