Exemestane for breast-cancer prevention in postmenopausal women
Paul E Goss, James N Ingle, José E Alés-Martínez, Angela M Cheung, Rowan T Chlebowski, Jean Wactawski-Wende, Anne McTiernan, John Robbins, Karen C Johnson, Lisa W Martin, Eric Winquist, Gloria E Sarto, Judy E Garber, Carol J Fabian, Pascal Pujol, Elizabeth Maunsell, Patricia Farmer, Karen A Gelmon, Dongsheng Tu, Harriet Richardson, NCIC CTG MAP.3 Study Investigators, P E Goss, J Ingle, J E Ales-Martinez, R Chlebowski, G Sarto, J Garber, C Fabian, H Richardson, E Maunsell, D Tu, P Farmer, P Goss, H Richardson, L Shepherd, A Hiltz, P O'Brien, Hugh M C Scarth, Louise Provencher, Pierre Dube, Marie-Helen Mayrand, Edgard Nassif, Conrad Falkson, Shailendra Verma, Barry Dworkin, James R Wright, Yasmin H Rahim, Angela Cheung, Andrea Eisen, Lavina Lickley, Eric W Winquist, Amanda Hey, Silvana Spadafora, Andrew L Cooke, Karen Gelmon, Susan Ellard, Nasrine Callet, Pierre-Francois Dupre, Nathalie Chabbert-Buffet, Tristan Gauthier, Pascaline Berthet, Pascal Pujol, Christelle Jouannaud, Amparo Ruiz, José Ignacio Chacón, Ana Lluch Hernández, Manuel Ramos, Jordi Xercavins, Elena Aguirre, Agustí Barnadas, Carlos Jara, José Enrique Alés, Santiago González, Arrate Plazaola, Jesús Florián, Raquel Andrés, Pedro Sánchez, Adolfo Frau, José Angel García, Pilar Zamora, Norberto Batista, José Manuel López, Miguel Ángel Seguí, Encarna Adrover, Gabriel Zanón, José Ignacio Tusquets, Joan Brunet, J Ignacio Blanco, Urricoechea, Manuel Ruiz Borrego, Mariscal, Álvaro Rodríguez, Miguel Méndez, Lourdes Calvo, Asunción Torres, Luis Robles, Emilio Alba, Antonio Piñero, Isabel Lorenzo, Encarnación González, Ana Miguel, Ma Isabel Calvo, Isabel Calvo, Purificación Martínez, Adolfo Murias, Mel Lorenzo, Antonio Antón, Juan de la Haba, Javier Cassinello, Angels Arcusa, Elisa García, Juan Bayo, César Rodriguez, Ma del Mar Muñoz, Blanca Hernando, Jesús García, Antonio Lorenzo Peñuelas, Andrés García, Albiol, Olufummilayo F Olopade, Misbah U Qadir, Richard C Frank, Susan Hendrix, Jeanne E Anderson, Anne McTiernan, Joseph A Sparano, John Robbins, Elizabeth Ann Shaughnessy, David Decker, Eli Avisar, Alejandra Perez-Tamayo, Pamela S Ganschow, Costas L Constantinou, Shelly S Lo, John Migas, Teresa Helsten, Susan Domchek, Rowan Chlebowski, Vanessa Barnabei, Antonella Rastelli, Jamie Claudio, Vanita R Aroda, Gloria E Sarto, Mansoor Saleh, Anna Marie Storniolo, Jose Sabino Aponte Pagan, Paul Goss, Anthony D Elias, Michele Cyr, Carol Fabian, Marie E Wood, Stephanie Hines, Lillian F Pliner, Carolyn Hendricks, William C Dooley, Kendrith M Rowland, Helen Krontiras, Sandhya Pruthi, Karen C Johnson, Judy E Garber, Rowell S Ashford 2nd, Lisa W Martin, Tracey F Weisberg, Molly A Brewer, Paul E Goss, James N Ingle, José E Alés-Martínez, Angela M Cheung, Rowan T Chlebowski, Jean Wactawski-Wende, Anne McTiernan, John Robbins, Karen C Johnson, Lisa W Martin, Eric Winquist, Gloria E Sarto, Judy E Garber, Carol J Fabian, Pascal Pujol, Elizabeth Maunsell, Patricia Farmer, Karen A Gelmon, Dongsheng Tu, Harriet Richardson, NCIC CTG MAP.3 Study Investigators, P E Goss, J Ingle, J E Ales-Martinez, R Chlebowski, G Sarto, J Garber, C Fabian, H Richardson, E Maunsell, D Tu, P Farmer, P Goss, H Richardson, L Shepherd, A Hiltz, P O'Brien, Hugh M C Scarth, Louise Provencher, Pierre Dube, Marie-Helen Mayrand, Edgard Nassif, Conrad Falkson, Shailendra Verma, Barry Dworkin, James R Wright, Yasmin H Rahim, Angela Cheung, Andrea Eisen, Lavina Lickley, Eric W Winquist, Amanda Hey, Silvana Spadafora, Andrew L Cooke, Karen Gelmon, Susan Ellard, Nasrine Callet, Pierre-Francois Dupre, Nathalie Chabbert-Buffet, Tristan Gauthier, Pascaline Berthet, Pascal Pujol, Christelle Jouannaud, Amparo Ruiz, José Ignacio Chacón, Ana Lluch Hernández, Manuel Ramos, Jordi Xercavins, Elena Aguirre, Agustí Barnadas, Carlos Jara, José Enrique Alés, Santiago González, Arrate Plazaola, Jesús Florián, Raquel Andrés, Pedro Sánchez, Adolfo Frau, José Angel García, Pilar Zamora, Norberto Batista, José Manuel López, Miguel Ángel Seguí, Encarna Adrover, Gabriel Zanón, José Ignacio Tusquets, Joan Brunet, J Ignacio Blanco, Urricoechea, Manuel Ruiz Borrego, Mariscal, Álvaro Rodríguez, Miguel Méndez, Lourdes Calvo, Asunción Torres, Luis Robles, Emilio Alba, Antonio Piñero, Isabel Lorenzo, Encarnación González, Ana Miguel, Ma Isabel Calvo, Isabel Calvo, Purificación Martínez, Adolfo Murias, Mel Lorenzo, Antonio Antón, Juan de la Haba, Javier Cassinello, Angels Arcusa, Elisa García, Juan Bayo, César Rodriguez, Ma del Mar Muñoz, Blanca Hernando, Jesús García, Antonio Lorenzo Peñuelas, Andrés García, Albiol, Olufummilayo F Olopade, Misbah U Qadir, Richard C Frank, Susan Hendrix, Jeanne E Anderson, Anne McTiernan, Joseph A Sparano, John Robbins, Elizabeth Ann Shaughnessy, David Decker, Eli Avisar, Alejandra Perez-Tamayo, Pamela S Ganschow, Costas L Constantinou, Shelly S Lo, John Migas, Teresa Helsten, Susan Domchek, Rowan Chlebowski, Vanessa Barnabei, Antonella Rastelli, Jamie Claudio, Vanita R Aroda, Gloria E Sarto, Mansoor Saleh, Anna Marie Storniolo, Jose Sabino Aponte Pagan, Paul Goss, Anthony D Elias, Michele Cyr, Carol Fabian, Marie E Wood, Stephanie Hines, Lillian F Pliner, Carolyn Hendricks, William C Dooley, Kendrith M Rowland, Helen Krontiras, Sandhya Pruthi, Karen C Johnson, Judy E Garber, Rowell S Ashford 2nd, Lisa W Martin, Tracey F Weisberg, Molly A Brewer
Abstract
Background: Tamoxifen and raloxifene have limited patient acceptance for primary prevention of breast cancer. Aromatase inhibitors prevent more contralateral breast cancers and cause fewer side effects than tamoxifen in patients with early-stage breast cancer.
Methods: In a randomized, placebo-controlled, double-blind trial of exemestane designed to detect a 65% relative reduction in invasive breast cancer, eligible postmenopausal women 35 years of age or older had at least one of the following risk factors: 60 years of age or older; Gail 5-year risk score greater than 1.66% (chances in 100 of invasive breast cancer developing within 5 years); prior atypical ductal or lobular hyperplasia or lobular carcinoma in situ; or ductal carcinoma in situ with mastectomy. Toxic effects and health-related and menopause-specific qualities of life were measured.
Results: A total of 4560 women for whom the median age was 62.5 years and the median Gail risk score was 2.3% were randomly assigned to either exemestane or placebo. At a median follow-up of 35 months, 11 invasive breast cancers were detected in those given exemestane and in 32 of those given placebo, with a 65% relative reduction in the annual incidence of invasive breast cancer (0.19% vs. 0.55%; hazard ratio, 0.35; 95% confidence interval [CI], 0.18 to 0.70; P=0.002). The annual incidence of invasive plus noninvasive (ductal carcinoma in situ) breast cancers was 0.35% on exemestane and 0.77% on placebo (hazard ratio, 0.47; 95% CI, 0.27 to 0.79; P=0.004). Adverse events occurred in 88% of the exemestane group and 85% of the placebo group (P=0.003), with no significant differences between the two groups in terms of skeletal fractures, cardiovascular events, other cancers, or treatment-related deaths. Minimal quality-of-life differences were observed.
Conclusions: Exemestane significantly reduced invasive breast cancers in postmenopausal women who were at moderately increased risk for breast cancer. During a median follow-up period of 3 years, exemestane was associated with no serious toxic effects and only minimal changes in health-related quality of life. (Funded by Pfizer and others; NCIC CTG MAP.3 ClinicalTrials.gov number, NCT00083174.).
Source: PubMed