Oestrogen plus progestin and lung cancer in postmenopausal women (Women's Health Initiative trial): a post-hoc analysis of a randomised controlled trial
Rowan T Chlebowski, Ann G Schwartz, Heather Wakelee, Garnet L Anderson, Marcia L Stefanick, JoAnn E Manson, Rebecca J Rodabough, Jason W Chien, Jean Wactawski-Wende, Margery Gass, Jane Morley Kotchen, Karen C Johnson, Mary Jo O'Sullivan, Judith K Ockene, Chu Chen, F Allan Hubbell, Women's Health Initiative Investigators, Elizabeth Nabel, Jacques Rossouw, Shari Ludlam, Joan McGowan, Nancy Geller, Leslie Ford, Ross Prentice, Garnet Anderson, Andrea LaCroix, Ruth Patterson, Anne McTiernan, Barbara Cochrane, Julie Hunt, Lesley Tinker, Charles Kooperberg, Martin McIntosh, C Y Wang, Chu Chen, Deborah Bowen, Alan Kristal, Janet Stanford, Nicole Urban, Noel Weiss, Emily White, Evan Stein, Peter Laskarzewski, Steven R Cummings, Michael Nevitt, Lisa Palermo, Lisa Harnack, Frank Cammarata, Steve Lindenfelser, Bruce Psaty, Susan Heckbert, Sylvia Wassertheil-Smoller, William Frishman, Judith Wylie-Rosett, David Barad, Ruth Freeman, Aleksandar Rajkovic, Jennifer Hays, Ronald Young, Haleh Sangi-Haghpeykar, JoAnn E Manson, Kathryn M Rexrode, Brian Walsh, J Michael Gaziano, Maria Bueche, Charles B Eaton, Michele Cyr, Gretchen Sloane, Lawrence Phillips, Vicki Butler, Vivian Porter, Shirley A A Beresford, Vicky M Taylor, Nancy F Woods, Maureen Henderson, Robyn Andersen, Lisa Martin, Judith Hsia, Nancy Gaba, Richard Katz, Rowan Chlebowski, Robert Detrano, Anita Nelson, Michele Geller, Yvonne Michael, Evelyn Whitlock, Victor Stevens, Njeri Karanja, Bette Caan, Stephen Sidney, Geri Bailey, Jane Hirata, Jane Morley Kotchen, Vanessa Barnabei, Theodore A Kotchen, Mary Ann C Gilligan, Joan Neuner, Barbara V Howard, Lucile Adams-Campbell, Lawrence Lessin, Cheryl Iglesia, Linda K Mickel, Linda Van Horn, Philip Greenland, Janardan Khandekar, Kiang Liu, Carol Rosenberg, Henry Black, Lynda Powell, Ellen Mason, Martha Gulati, Marcia L Stefanick, Mark A Hlatky, Bertha Chen, Randall S Stafford, Sally Mackey, Dorothy Lane, Iris Granek, William Lawson, Catherine Messina, Gabriel San Roman, Rebecca Jackson, Randall Harris, Electra Paskett, W Jerry Mysiw, Michael Blumenfeld, Cora E Lewis, Albert Oberman, James M Shikany, Monika Safford, Cynthia A Thomson, Tamsen Bassford, Cheryl Ritenbaugh, Zhao Chen, Marcia Ko, Jean Wactawski-Wende, Maurizio Trevisan, Ellen Smit, Susan Graham, June Chang, John Robbins, S Yasmeen, F Allan Hubbell, Gail Frank, Nathan Wong, Nancy Greep, Bradley Monk, Lauren Nathan, David Heber, Robert Elashoff, Simin Liu, Robert D Langer, Michael H Criqui, Gregory T Talavera, Cedric F Garland, Matthew A Allison, Margery Gass, Nelson Watts, Marian Limacher, Michael Perri, Andrew Kaunitz, R Stan Williams, Yvonne Brinson, J David Curb, Helen Petrovitch, Beatriz Rodriguez, Kamal Masaki, Patricia Blanchette, Robert Wallace, James Torner, Susan Johnson, Linda Snetselaar, Jennifer Robinson, Judith Ockene, Milagros Rosal, Ira Ockene, Robert Yood, Patricia Aronson, Norman Lasser, Baljinder Singh, Vera Lasser, John Kostis, Peter McGovern, Mary Jo O'Sullivan, Linda Parker, JoNell Potter, Diann Fernandez, Pat Caralis, Karen L Margolis, Richard H Grimm, Mary F Perron, Cynthia Bjerk, Sarah Kempainen, Robert Brunner, William Graettinger, Vicki Oujevolk, Michael Bloch, Gerardo Heiss, Pamela Haines, David Ontjes, Carla Sueta, Ellen Wells, Lewis Kuller, Jane Cauley, N Carole Milas, Karen C Johnson, Suzanne Satterfield, Rongling Li, Stephanie Connelly, Fran Tylavsky, Robert Brzyski, Robert Schenken, Gloria E Sarto, Douglas Laube, Patrick McBride, Julie Mares, Barbara Loevinger, Mara Vitolins, Greg Burke, Robin Crouse, Scott Washburn, Michael Simon, Jennifer Hays, Foreyt Foreyt, Annlouise R Assaf, Dallas Hall, Valery Miller, Barbara Valanis, Robert Hiatt, Carolyn Clifford, Linda Pottern, Frank Meyskens Jr, Howard Judd, James Liu, Nelson Watts, Marianna Baum, Richard Grimm, Sandra Daugherty, David Sheps, Barbara Hulka, William Applegate, Catherine Allen, Denise Bonds, Rowan T Chlebowski, Ann G Schwartz, Heather Wakelee, Garnet L Anderson, Marcia L Stefanick, JoAnn E Manson, Rebecca J Rodabough, Jason W Chien, Jean Wactawski-Wende, Margery Gass, Jane Morley Kotchen, Karen C Johnson, Mary Jo O'Sullivan, Judith K Ockene, Chu Chen, F Allan Hubbell, Women's Health Initiative Investigators, Elizabeth Nabel, Jacques Rossouw, Shari Ludlam, Joan McGowan, Nancy Geller, Leslie Ford, Ross Prentice, Garnet Anderson, Andrea LaCroix, Ruth Patterson, Anne McTiernan, Barbara Cochrane, Julie Hunt, Lesley Tinker, Charles Kooperberg, Martin McIntosh, C Y Wang, Chu Chen, Deborah Bowen, Alan Kristal, Janet Stanford, Nicole Urban, Noel Weiss, Emily White, Evan Stein, Peter Laskarzewski, Steven R Cummings, Michael Nevitt, Lisa Palermo, Lisa Harnack, Frank Cammarata, Steve Lindenfelser, Bruce Psaty, Susan Heckbert, Sylvia Wassertheil-Smoller, William Frishman, Judith Wylie-Rosett, David Barad, Ruth Freeman, Aleksandar Rajkovic, Jennifer Hays, Ronald Young, Haleh Sangi-Haghpeykar, JoAnn E Manson, Kathryn M Rexrode, Brian Walsh, J Michael Gaziano, Maria Bueche, Charles B Eaton, Michele Cyr, Gretchen Sloane, Lawrence Phillips, Vicki Butler, Vivian Porter, Shirley A A Beresford, Vicky M Taylor, Nancy F Woods, Maureen Henderson, Robyn Andersen, Lisa Martin, Judith Hsia, Nancy Gaba, Richard Katz, Rowan Chlebowski, Robert Detrano, Anita Nelson, Michele Geller, Yvonne Michael, Evelyn Whitlock, Victor Stevens, Njeri Karanja, Bette Caan, Stephen Sidney, Geri Bailey, Jane Hirata, Jane Morley Kotchen, Vanessa Barnabei, Theodore A Kotchen, Mary Ann C Gilligan, Joan Neuner, Barbara V Howard, Lucile Adams-Campbell, Lawrence Lessin, Cheryl Iglesia, Linda K Mickel, Linda Van Horn, Philip Greenland, Janardan Khandekar, Kiang Liu, Carol Rosenberg, Henry Black, Lynda Powell, Ellen Mason, Martha Gulati, Marcia L Stefanick, Mark A Hlatky, Bertha Chen, Randall S Stafford, Sally Mackey, Dorothy Lane, Iris Granek, William Lawson, Catherine Messina, Gabriel San Roman, Rebecca Jackson, Randall Harris, Electra Paskett, W Jerry Mysiw, Michael Blumenfeld, Cora E Lewis, Albert Oberman, James M Shikany, Monika Safford, Cynthia A Thomson, Tamsen Bassford, Cheryl Ritenbaugh, Zhao Chen, Marcia Ko, Jean Wactawski-Wende, Maurizio Trevisan, Ellen Smit, Susan Graham, June Chang, John Robbins, S Yasmeen, F Allan Hubbell, Gail Frank, Nathan Wong, Nancy Greep, Bradley Monk, Lauren Nathan, David Heber, Robert Elashoff, Simin Liu, Robert D Langer, Michael H Criqui, Gregory T Talavera, Cedric F Garland, Matthew A Allison, Margery Gass, Nelson Watts, Marian Limacher, Michael Perri, Andrew Kaunitz, R Stan Williams, Yvonne Brinson, J David Curb, Helen Petrovitch, Beatriz Rodriguez, Kamal Masaki, Patricia Blanchette, Robert Wallace, James Torner, Susan Johnson, Linda Snetselaar, Jennifer Robinson, Judith Ockene, Milagros Rosal, Ira Ockene, Robert Yood, Patricia Aronson, Norman Lasser, Baljinder Singh, Vera Lasser, John Kostis, Peter McGovern, Mary Jo O'Sullivan, Linda Parker, JoNell Potter, Diann Fernandez, Pat Caralis, Karen L Margolis, Richard H Grimm, Mary F Perron, Cynthia Bjerk, Sarah Kempainen, Robert Brunner, William Graettinger, Vicki Oujevolk, Michael Bloch, Gerardo Heiss, Pamela Haines, David Ontjes, Carla Sueta, Ellen Wells, Lewis Kuller, Jane Cauley, N Carole Milas, Karen C Johnson, Suzanne Satterfield, Rongling Li, Stephanie Connelly, Fran Tylavsky, Robert Brzyski, Robert Schenken, Gloria E Sarto, Douglas Laube, Patrick McBride, Julie Mares, Barbara Loevinger, Mara Vitolins, Greg Burke, Robin Crouse, Scott Washburn, Michael Simon, Jennifer Hays, Foreyt Foreyt, Annlouise R Assaf, Dallas Hall, Valery Miller, Barbara Valanis, Robert Hiatt, Carolyn Clifford, Linda Pottern, Frank Meyskens Jr, Howard Judd, James Liu, Nelson Watts, Marianna Baum, Richard Grimm, Sandra Daugherty, David Sheps, Barbara Hulka, William Applegate, Catherine Allen, Denise Bonds
Abstract
Background: In the post-intervention period of the Women's Health Initiative (WHI) trial, women assigned to treatment with oestrogen plus progestin had a higher risk of cancer than did those assigned to placebo. Results also suggested that the combined hormone therapy might increase mortality from lung cancer. To assess whether such an association exists, we undertook a post-hoc analysis of lung cancers diagnosed in the trial over the entire follow-up period.
Methods: The WHI study was a randomised, double-blind, placebo-controlled trial undertaken in 40 centres in the USA. 16 608 postmenopausal women aged 50-79 years with an intact uterus were randomly assigned by a computerised, stratified, permuted block algorithm to receive a once-daily tablet of 0.625 mg conjugated equine oestrogen plus 2.5 mg medroxyprogesterone acetate (n=8506) or matching placebo (n=8102). We assessed incidence and mortality rates for all lung cancer, small-cell lung cancer, and non-small-cell lung cancer by use of data from treatment and post-intervention follow-up periods. Analysis was by intention to treat. This study is registered with ClinicalTrials.gov, number NCT00000611.
Findings: After a mean of 5.6 years (SD 1.3) of treatment and 2.4 years (0.4) of additional follow-up, 109 women in the combined hormone therapy group had been diagnosed with lung cancer compared with 85 in the placebo group (incidence per year 0.16%vs 0.13%; hazard ratio [HR] 1.23, 95% CI 0.92-1.63, p=0.16). 96 women assigned to combined therapy had non-small-cell lung cancer compared with 72 assigned to placebo (0.14%vs 0.11%; HR 1.28, 0.94-1.73, p=0.12). More women died from lung cancer in the combined hormone therapy group than in the placebo group (73 vs 40 deaths; 0.11%vs 0.06%; HR 1.71, 1.16-2.52, p=0.01), mainly as a result of a higher number of deaths from non-small-cell lung cancer in the combined therapy group (62 vs 31 deaths; 0.09%vs 0.05%; HR 1.87, 1.22-2.88, p=0.004). Incidence and mortality rates of small-cell lung cancer were similar between groups.
Interpretation: Although treatment with oestrogen plus progestin in postmenopausal women did not increase incidence of lung cancer, it increased the number of deaths from lung cancer, in particular deaths from non-small-cell lung cancer. These findings should be incorporated into risk-benefit discussions with women considering combined hormone therapy, especially those with a high risk of lung cancer.
Funding: National Heart, Lung and Blood Institute, National Institutes of Health.
Conflict of interest statement
Conflicts of Interest
RTC has received speaker’s fee and honorarium for advisory boards and consulting from AstraZeneca, Novartis; honorarium for advisory boards and consulting for Lilly, Amgen and Pfizer and grant support from Amgen. RTC, GLA, MLS. JEM, JW, MG, JMK, KCJ, MJO, JKO and FAH have received grant support from NIH; KCJ and RTC additionally have received grant support from the National Cancer Institute of Canada. MG has received grant support from Wyeth. AGS, HW, RJR, JWC and CC have no conflicts of interest.
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Source: PubMed