Tumor phenotype and breast density in distinct categories of interval cancer: Results of population-based mammography screening in Spain

Laia Domingo; Dolores Salas; Raquel Zubizarreta; Marisa Baré; Garbiñe Sarriugarte; Teresa Barata; Josefa Ibáñez; Jordi Blanch; Montserrat Puig-Vives; Ana B. Fernández; Xavier Castells; Maria Sala; Mercè Comas; Francesc Macià; Juan Martínez; Ana Rodríguez-Arana; Marta Román; Anabel Romero; Carmen Alberich; María Casals; Amparo Lluch; Inmaculada Martínez; Josefa Miranda; Javier Morales; Ana Torrella; Raquel Almazán; Miguel Conde; Montserrat Corujo; Joaquín Mosquera; Alicia Sarandeses; Manuel Vázquez; Isabel Díez de la Lastra; Juana María Reyes; Arantza Otegi; Núria Torà; Joana Ferrer; Francesc Castanyer; Gemma Renart; Rafael Marcos-Gragera; Carles Forné; Montserrat Martínez-Alonso; Albert Roso; Montse Rué; Ester Vilaprinyó; Misericordia Carles; Aleix Gregori; María José Pérez; Roger Pla

doi:10.1186/bcr3595

Tumor phenotype and breast density in distinct categories of interval cancer: Results of population-based mammography screening in Spain

Laia Domingo, Dolores Salas, Raquel Zubizarreta, Marisa Baré, Garbiñe Sarriugarte, Teresa Barata, Josefa Ibáñez, Jordi Blanch, Montserrat Puig-Vives, Ana B. Fernández, Xavier Castells, Maria Sala, Mercè Comas, Francesc Macià, Juan Martínez, Ana Rodríguez-Arana, Marta Román, Anabel Romero, Carmen Alberich, María CasalsAmparo Lluch, Inmaculada Martínez, Josefa Miranda, Javier Morales, Ana Torrella, Raquel Almazán, Miguel Conde, Montserrat Corujo, Joaquín Mosquera, Alicia Sarandeses, Manuel Vázquez, Isabel Díez de la Lastra, Juana María Reyes, Arantza Otegi, Núria Torà, Joana Ferrer, Francesc Castanyer, Gemma Renart, Rafael Marcos-Gragera, Carles Forné, Montserrat Martínez-Alonso, Albert Roso, Montse Rué, Ester Vilaprinyó, Misericordia Carles, Aleix Gregori, María José Pérez, Roger Pla

Research output: Contribution to journal › Article › Research › peer-review

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Abstract

Introduction: Interval cancers are tumors arising after a negative screening episode and before the next screening invitation. They can be classified into true interval cancers, false-negatives, minimal-sign cancers, and occult tumors based on mammographic findings in screening and diagnostic mammograms. This study aimed to describe tumor-related characteristics and the association of breast density and tumor phenotype within four interval cancer categories.Methods: We included 2,245 invasive tumors (1,297 screening-detected and 948 interval cancers) diagnosed from 2000 to 2009 among 645,764 women aged 45 to 69 who underwent biennial screening in Spain. Interval cancers were classified by a semi-informed retrospective review into true interval cancers (n = 455), false-negatives (n = 224), minimal-sign (n = 166), and occult tumors (n = 103). Breast density was evaluated using Boyd's scale and was conflated into: <25%; 25 to 50%; 50 to 75%; >75%. Tumor-related information was obtained from cancer registries and clinical records. Tumor phenotype was defined as follows: luminal A: ER+/HER2- or PR+/HER2-; luminal B: ER+/HER2+ or PR+/HER2+; HER2: ER-/PR-/HER2+; triple-negative: ER-/PR-/HER2- The association of tumor phenotype and breast density was assessed using a multinomial logistic regression model. Adjusted odds ratios (OR) and 95% confidence intervals (95% CI) were calculated. All statistical tests were two-sided.Results: Forty-eight percent of interval cancers were true interval cancers and 23.6% false-negatives. True interval cancers were associated with HER2 and triple-negative phenotypes (OR = 1.91 (95% CI:1.22-2.96), OR = 2.07 (95% CI:1.42-3.01), respectively) and extremely dense breasts (>75%) (OR = 1.67 (95% CI:1.08-2.56)). However, among true interval cancers a higher proportion of triple-negative tumors was observed in predominantly fatty breasts (<25%) than in denser breasts (28.7%, 21.4%, 11.3% and 14.3%, respectively; <0.001). False-negatives and occult tumors had similar phenotypic characteristics to screening-detected cancers, extreme breast density being strongly associated with occult tumors (OR = 6.23 (95% CI:2.65-14.66)). Minimal-sign cancers were biologically close to true interval cancers but showed no association with breast density.Conclusions: Our findings revealed that both the distribution of tumor phenotype and breast density play specific and independent roles in each category of interval cancer. Further research is needed to understand the biological basis of the overrepresentation of triple-negative phenotype among predominantly fatty breasts in true interval cancers. © 2014 Domingo et al.; licensee BioMed Central Ltd.

Original language	English
Article number	R3
Journal	Breast Cancer Research
Volume	16
Issue number	1
DOIs	https://doi.org/10.1186/bcr3595
Publication status	Published - 10 Jan 2014

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Domingo, L., Salas, D., Zubizarreta, R., Baré, M., Sarriugarte, G., Barata, T., Ibáñez, J., Blanch, J., Puig-Vives, M., Fernández, A. B., Castells, X., Sala, M., Comas, M., Macià, F., Martínez, J., Rodríguez-Arana, A., Román, M., Romero, A., Alberich, C., ... Pla, R. (2014). Tumor phenotype and breast density in distinct categories of interval cancer: Results of population-based mammography screening in Spain. Breast Cancer Research, 16(1), [R3]. https://doi.org/10.1186/bcr3595

Domingo, Laia ; Salas, Dolores ; Zubizarreta, Raquel ; Baré, Marisa ; Sarriugarte, Garbiñe ; Barata, Teresa ; Ibáñez, Josefa ; Blanch, Jordi ; Puig-Vives, Montserrat ; Fernández, Ana B. ; Castells, Xavier ; Sala, Maria ; Comas, Mercè ; Macià, Francesc ; Martínez, Juan ; Rodríguez-Arana, Ana ; Román, Marta ; Romero, Anabel ; Alberich, Carmen ; Casals, María ; Lluch, Amparo ; Martínez, Inmaculada ; Miranda, Josefa ; Morales, Javier ; Torrella, Ana ; Almazán, Raquel ; Conde, Miguel ; Corujo, Montserrat ; Mosquera, Joaquín ; Sarandeses, Alicia ; Vázquez, Manuel ; de la Lastra, Isabel Díez ; Reyes, Juana María ; Otegi, Arantza ; Torà, Núria ; Ferrer, Joana ; Castanyer, Francesc ; Renart, Gemma ; Marcos-Gragera, Rafael ; Forné, Carles ; Martínez-Alonso, Montserrat ; Roso, Albert ; Rué, Montse ; Vilaprinyó, Ester ; Carles, Misericordia ; Gregori, Aleix ; Pérez, María José ; Pla, Roger. / Tumor phenotype and breast density in distinct categories of interval cancer: Results of population-based mammography screening in Spain. In: Breast Cancer Research. 2014 ; Vol. 16, No. 1.

@article{0e3888fa4f75491092790d74441b577e,

title = "Tumor phenotype and breast density in distinct categories of interval cancer: Results of population-based mammography screening in Spain",

abstract = "Introduction: Interval cancers are tumors arising after a negative screening episode and before the next screening invitation. They can be classified into true interval cancers, false-negatives, minimal-sign cancers, and occult tumors based on mammographic findings in screening and diagnostic mammograms. This study aimed to describe tumor-related characteristics and the association of breast density and tumor phenotype within four interval cancer categories.Methods: We included 2,245 invasive tumors (1,297 screening-detected and 948 interval cancers) diagnosed from 2000 to 2009 among 645,764 women aged 45 to 69 who underwent biennial screening in Spain. Interval cancers were classified by a semi-informed retrospective review into true interval cancers (n = 455), false-negatives (n = 224), minimal-sign (n = 166), and occult tumors (n = 103). Breast density was evaluated using Boyd's scale and was conflated into: <25%; 25 to 50%; 50 to 75%; >75%. Tumor-related information was obtained from cancer registries and clinical records. Tumor phenotype was defined as follows: luminal A: ER+/HER2- or PR+/HER2-; luminal B: ER+/HER2+ or PR+/HER2+; HER2: ER-/PR-/HER2+; triple-negative: ER-/PR-/HER2- The association of tumor phenotype and breast density was assessed using a multinomial logistic regression model. Adjusted odds ratios (OR) and 95% confidence intervals (95% CI) were calculated. All statistical tests were two-sided.Results: Forty-eight percent of interval cancers were true interval cancers and 23.6% false-negatives. True interval cancers were associated with HER2 and triple-negative phenotypes (OR = 1.91 (95% CI:1.22-2.96), OR = 2.07 (95% CI:1.42-3.01), respectively) and extremely dense breasts (>75%) (OR = 1.67 (95% CI:1.08-2.56)). However, among true interval cancers a higher proportion of triple-negative tumors was observed in predominantly fatty breasts (<25%) than in denser breasts (28.7%, 21.4%, 11.3% and 14.3%, respectively; <0.001). False-negatives and occult tumors had similar phenotypic characteristics to screening-detected cancers, extreme breast density being strongly associated with occult tumors (OR = 6.23 (95% CI:2.65-14.66)). Minimal-sign cancers were biologically close to true interval cancers but showed no association with breast density.Conclusions: Our findings revealed that both the distribution of tumor phenotype and breast density play specific and independent roles in each category of interval cancer. Further research is needed to understand the biological basis of the overrepresentation of triple-negative phenotype among predominantly fatty breasts in true interval cancers. {\textcopyright} 2014 Domingo et al.; licensee BioMed Central Ltd.",

author = "Laia Domingo and Dolores Salas and Raquel Zubizarreta and Marisa Bar{\'e} and Garbi{\~n}e Sarriugarte and Teresa Barata and Josefa Ib{\'a}{\~n}ez and Jordi Blanch and Montserrat Puig-Vives and Fern{\'a}ndez, {Ana B.} and Xavier Castells and Maria Sala and Merc{\`e} Comas and Francesc Maci{\`a} and Juan Mart{\'i}nez and Ana Rodr{\'i}guez-Arana and Marta Rom{\'a}n and Anabel Romero and Carmen Alberich and Mar{\'i}a Casals and Amparo Lluch and Inmaculada Mart{\'i}nez and Josefa Miranda and Javier Morales and Ana Torrella and Raquel Almaz{\'a}n and Miguel Conde and Montserrat Corujo and Joaqu{\'i}n Mosquera and Alicia Sarandeses and Manuel V{\'a}zquez and {de la Lastra}, {Isabel D{\'i}ez} and Reyes, {Juana Mar{\'i}a} and Arantza Otegi and N{\'u}ria Tor{\`a} and Joana Ferrer and Francesc Castanyer and Gemma Renart and Rafael Marcos-Gragera and Carles Forn{\'e} and Montserrat Mart{\'i}nez-Alonso and Albert Roso and Montse Ru{\'e} and Ester Vilapriny{\'o} and Misericordia Carles and Aleix Gregori and P{\'e}rez, {Mar{\'i}a Jos{\'e}} and Roger Pla",

year = "2014",

month = jan,

day = "10",

doi = "10.1186/bcr3595",

language = "English",

volume = "16",

number = "1",

}

Domingo, L, Salas, D, Zubizarreta, R, Baré, M, Sarriugarte, G, Barata, T, Ibáñez, J, Blanch, J, Puig-Vives, M, Fernández, AB, Castells, X, Sala, M, Comas, M, Macià, F, Martínez, J, Rodríguez-Arana, A, Román, M, Romero, A, Alberich, C, Casals, M, Lluch, A, Martínez, I, Miranda, J, Morales, J, Torrella, A, Almazán, R, Conde, M, Corujo, M, Mosquera, J, Sarandeses, A, Vázquez, M, de la Lastra, ID, Reyes, JM, Otegi, A, Torà, N, Ferrer, J, Castanyer, F, Renart, G, Marcos-Gragera, R, Forné, C, Martínez-Alonso, M, Roso, A, Rué, M, Vilaprinyó, E, Carles, M, Gregori, A, Pérez, MJ & Pla, R 2014, 'Tumor phenotype and breast density in distinct categories of interval cancer: Results of population-based mammography screening in Spain', Breast Cancer Research, vol. 16, no. 1, R3. https://doi.org/10.1186/bcr3595

Tumor phenotype and breast density in distinct categories of interval cancer: Results of population-based mammography screening in Spain. / Domingo, Laia; Salas, Dolores; Zubizarreta, Raquel; Baré, Marisa; Sarriugarte, Garbiñe; Barata, Teresa; Ibáñez, Josefa; Blanch, Jordi; Puig-Vives, Montserrat; Fernández, Ana B.; Castells, Xavier; Sala, Maria; Comas, Mercè; Macià, Francesc; Martínez, Juan; Rodríguez-Arana, Ana; Román, Marta; Romero, Anabel; Alberich, Carmen; Casals, María; Lluch, Amparo; Martínez, Inmaculada; Miranda, Josefa; Morales, Javier; Torrella, Ana; Almazán, Raquel; Conde, Miguel; Corujo, Montserrat; Mosquera, Joaquín; Sarandeses, Alicia; Vázquez, Manuel; de la Lastra, Isabel Díez; Reyes, Juana María; Otegi, Arantza; Torà, Núria; Ferrer, Joana; Castanyer, Francesc; Renart, Gemma; Marcos-Gragera, Rafael; Forné, Carles; Martínez-Alonso, Montserrat; Roso, Albert; Rué, Montse; Vilaprinyó, Ester; Carles, Misericordia; Gregori, Aleix; Pérez, María José; Pla, Roger.

In: Breast Cancer Research, Vol. 16, No. 1, R3, 10.01.2014.

Research output: Contribution to journal › Article › Research › peer-review

TY - JOUR

T1 - Tumor phenotype and breast density in distinct categories of interval cancer: Results of population-based mammography screening in Spain

AU - Domingo, Laia

AU - Salas, Dolores

AU - Zubizarreta, Raquel

AU - Baré, Marisa

AU - Sarriugarte, Garbiñe

AU - Barata, Teresa

AU - Ibáñez, Josefa

AU - Blanch, Jordi

AU - Puig-Vives, Montserrat

AU - Fernández, Ana B.

AU - Castells, Xavier

AU - Sala, Maria

AU - Comas, Mercè

AU - Macià, Francesc

AU - Martínez, Juan

AU - Rodríguez-Arana, Ana

AU - Román, Marta

AU - Romero, Anabel

AU - Alberich, Carmen

AU - Casals, María

AU - Lluch, Amparo

AU - Martínez, Inmaculada

AU - Miranda, Josefa

AU - Morales, Javier

AU - Torrella, Ana

AU - Almazán, Raquel

AU - Conde, Miguel

AU - Corujo, Montserrat

AU - Mosquera, Joaquín

AU - Sarandeses, Alicia

AU - Vázquez, Manuel

AU - de la Lastra, Isabel Díez

AU - Reyes, Juana María

AU - Otegi, Arantza

AU - Torà, Núria

AU - Ferrer, Joana

AU - Castanyer, Francesc

AU - Renart, Gemma

AU - Marcos-Gragera, Rafael

AU - Forné, Carles

AU - Martínez-Alonso, Montserrat

AU - Roso, Albert

AU - Rué, Montse

AU - Vilaprinyó, Ester

AU - Carles, Misericordia

AU - Gregori, Aleix

AU - Pérez, María José

AU - Pla, Roger

PY - 2014/1/10

Y1 - 2014/1/10

N2 - Introduction: Interval cancers are tumors arising after a negative screening episode and before the next screening invitation. They can be classified into true interval cancers, false-negatives, minimal-sign cancers, and occult tumors based on mammographic findings in screening and diagnostic mammograms. This study aimed to describe tumor-related characteristics and the association of breast density and tumor phenotype within four interval cancer categories.Methods: We included 2,245 invasive tumors (1,297 screening-detected and 948 interval cancers) diagnosed from 2000 to 2009 among 645,764 women aged 45 to 69 who underwent biennial screening in Spain. Interval cancers were classified by a semi-informed retrospective review into true interval cancers (n = 455), false-negatives (n = 224), minimal-sign (n = 166), and occult tumors (n = 103). Breast density was evaluated using Boyd's scale and was conflated into: <25%; 25 to 50%; 50 to 75%; >75%. Tumor-related information was obtained from cancer registries and clinical records. Tumor phenotype was defined as follows: luminal A: ER+/HER2- or PR+/HER2-; luminal B: ER+/HER2+ or PR+/HER2+; HER2: ER-/PR-/HER2+; triple-negative: ER-/PR-/HER2- The association of tumor phenotype and breast density was assessed using a multinomial logistic regression model. Adjusted odds ratios (OR) and 95% confidence intervals (95% CI) were calculated. All statistical tests were two-sided.Results: Forty-eight percent of interval cancers were true interval cancers and 23.6% false-negatives. True interval cancers were associated with HER2 and triple-negative phenotypes (OR = 1.91 (95% CI:1.22-2.96), OR = 2.07 (95% CI:1.42-3.01), respectively) and extremely dense breasts (>75%) (OR = 1.67 (95% CI:1.08-2.56)). However, among true interval cancers a higher proportion of triple-negative tumors was observed in predominantly fatty breasts (<25%) than in denser breasts (28.7%, 21.4%, 11.3% and 14.3%, respectively; <0.001). False-negatives and occult tumors had similar phenotypic characteristics to screening-detected cancers, extreme breast density being strongly associated with occult tumors (OR = 6.23 (95% CI:2.65-14.66)). Minimal-sign cancers were biologically close to true interval cancers but showed no association with breast density.Conclusions: Our findings revealed that both the distribution of tumor phenotype and breast density play specific and independent roles in each category of interval cancer. Further research is needed to understand the biological basis of the overrepresentation of triple-negative phenotype among predominantly fatty breasts in true interval cancers. © 2014 Domingo et al.; licensee BioMed Central Ltd.

AB - Introduction: Interval cancers are tumors arising after a negative screening episode and before the next screening invitation. They can be classified into true interval cancers, false-negatives, minimal-sign cancers, and occult tumors based on mammographic findings in screening and diagnostic mammograms. This study aimed to describe tumor-related characteristics and the association of breast density and tumor phenotype within four interval cancer categories.Methods: We included 2,245 invasive tumors (1,297 screening-detected and 948 interval cancers) diagnosed from 2000 to 2009 among 645,764 women aged 45 to 69 who underwent biennial screening in Spain. Interval cancers were classified by a semi-informed retrospective review into true interval cancers (n = 455), false-negatives (n = 224), minimal-sign (n = 166), and occult tumors (n = 103). Breast density was evaluated using Boyd's scale and was conflated into: <25%; 25 to 50%; 50 to 75%; >75%. Tumor-related information was obtained from cancer registries and clinical records. Tumor phenotype was defined as follows: luminal A: ER+/HER2- or PR+/HER2-; luminal B: ER+/HER2+ or PR+/HER2+; HER2: ER-/PR-/HER2+; triple-negative: ER-/PR-/HER2- The association of tumor phenotype and breast density was assessed using a multinomial logistic regression model. Adjusted odds ratios (OR) and 95% confidence intervals (95% CI) were calculated. All statistical tests were two-sided.Results: Forty-eight percent of interval cancers were true interval cancers and 23.6% false-negatives. True interval cancers were associated with HER2 and triple-negative phenotypes (OR = 1.91 (95% CI:1.22-2.96), OR = 2.07 (95% CI:1.42-3.01), respectively) and extremely dense breasts (>75%) (OR = 1.67 (95% CI:1.08-2.56)). However, among true interval cancers a higher proportion of triple-negative tumors was observed in predominantly fatty breasts (<25%) than in denser breasts (28.7%, 21.4%, 11.3% and 14.3%, respectively; <0.001). False-negatives and occult tumors had similar phenotypic characteristics to screening-detected cancers, extreme breast density being strongly associated with occult tumors (OR = 6.23 (95% CI:2.65-14.66)). Minimal-sign cancers were biologically close to true interval cancers but showed no association with breast density.Conclusions: Our findings revealed that both the distribution of tumor phenotype and breast density play specific and independent roles in each category of interval cancer. Further research is needed to understand the biological basis of the overrepresentation of triple-negative phenotype among predominantly fatty breasts in true interval cancers. © 2014 Domingo et al.; licensee BioMed Central Ltd.

U2 - 10.1186/bcr3595

DO - 10.1186/bcr3595

M3 - Article

VL - 16

IS - 1

M1 - R3

ER -