Why does oestrogen-only hormone therapy have such a small impact on breast cancer risk? A hypothesis

References

• Trichopoulos D, Adami HO, Ekbom A, Hsieh CC, Lagiou P.Early life events and conditions and breast cancer risk: from epidemiology to etiology. In J Cancer 2008;122:481–485.
   PubMed Web of Science ®Google Scholar
• Lin NU, Winer EP.Advances in adjuvant endocrine therapy for postmenopausal women. J Clin Oncol 2008;26:798–805.
   PubMed Web of Science ®Google Scholar
• Greiser CM, Greiser EM, Dören M.Menopausal hormone therapy and risk of breast cancer: a meta-analysis of epidemiological studies and randomized controlled trials. Hum Reprod Update 2005;11(6):561–573, 2005.
   PubMed Web of Science ®Google Scholar
• Chen FP.Postmenopausal hormone therapy and risk of breast cancer. Chang Gung Med J 2009;32:140–147.
   PubMedGoogle Scholar
• Cusack J.Hormone replacement therapy. Euro J Cancer 2008;44:2344–2349.
   PubMed Web of Science ®Google Scholar
• The Women's Health Initiative Steering Committee. Effects of conjugated equine estrogen in postmenopausal women with hysterectomy. The Women's Health Initiative randomized controlled trial. JAMA 2004;291:1701–1712.
   PubMed Web of Science ®Google Scholar
• Stefanick ML, Anderson GL, Margolis KL, Hendrix SL, Rodabough RJ, Paskett ED, Lane DS, Hubbell FA, Assaf AR, Sarto GE, Schenken RS, Yasmeen S, Lessin L, Chlebowski RT.Effects of conjugated equine estrogens on breast cancer and mammography screening in postmenopausal women with hysterectomy. JAMA 2006;295:1647–1657.
   PubMed Web of Science ®Google Scholar
• Zhang SM, Manson JE, Rexrode KM, Cook NR, Buring JE, Lee IM.Use of conjugated estrogen alone and risk of breast cancer. Am J Epidemiol 2007;165:524–529.
   PubMed Web of Science ®Google Scholar
• Beral V, for the MillionWomen Study Collaborators. Breast cancer and hormone-replacement therapy in the Million Women Study. Lancet 2003;362:419–427.
   PubMed Web of Science ®Google Scholar
• Shapiro S.The Million Women Study: potential biases do not allow uncritical acceptance of the data. Climacteric 2004;7(1):3–7.
   PubMed Web of Science ®Google Scholar
• Cummings SR, Ettinger B, Delmas PD, Kenemans P, Stathopoulos V, Verweij P, Mol-Arts M, Kloosterboer L, Mosca L, Christiansen C, Bilezikian J, Kerzberg EM, Johnson S, Zanchetta J, Grobbee DE, Seifert W, Eastell R.The effects of Tibolone in older postmenopausal women. N Engl J Med 2008;359:697–708.
   PubMed Web of Science ®Google Scholar
• Kenemans P, Bundred NJ, Foidart JM, Kubista E, von Schoultz B, Sismondi P, Vassilopoulou-Sellin R, Yip CH, Egberts J, Mol-Arts M, Mulder R, van Os S, Beckmann MW.Safety and efficacy of tibolone in breast-cancer patients with vasomotor symptoms: a double-blind, randomised, non-inferiority trial. Lancet Oncology 2009;10(2):135–146.
   PubMed Web of Science ®Google Scholar
• Chen YC, Manson JE, Hankinson SE, Rosner B, Holmes MD, Willett WC, Colditz GA.Unopposed estrogen therapy and the risk of invasive breast cancer. Arch Intern Med 2006;166:1027–1032.
   PubMed Web of Science ®Google Scholar
• Russo J, Russo IH.Development of the human breast. Maturitas 2004;49:2–15.
   PubMed Web of Science ®Google Scholar
• Baik I, Becker PS, DeVito WJ, Lagiou P, Ballen K, Quesenberry PJ, Hsieh CC.Stem cells and prenatal origin of breast cancer. Cancer Causes Control 2004;15:517–530.
   PubMed Web of Science ®Google Scholar
• Kalirai H, Clarke RB.Human breast epithelial stem cells and their regulation. J Pathol 2006;208:7–16.
   PubMed Web of Science ®Google Scholar
• Al-Hajj M, Wicha MS, Benito-Hernandez A, Morrison SJ, Clarke MF.Prospective identification of tumorigenic breast cancer cells. Proc Natl Acad Sci USA 2003;100:3983–3988.
   PubMed Web of Science ®Google Scholar
• Shackleton M, Vaillant F, Simpson KJ, Stingl J, Smyth GK, Asselin-Labat ML, Wu L, Lindeman GJ, Visvader JE.Generation of a functional mammary gland from a single stem cell. Nature 2006;439:84–88.
   PubMed Web of Science ®Google Scholar
• Kenney NJ, Smith GH, Lawrence E, Barrett JC, Salomon DS.Identification of stem cell units in the terminal end bud and duct of the mouse mammary gland. J Biomed Biotechnol 2001;1:133–143.
   PubMedGoogle Scholar
• Dontu G, El-Ashry D, Wicha M.Breast cancer, stem/progenitor cells and the estrogen receptor. Trends Endocrinol Metab 2004;15(5):193–197.
   PubMed Web of Science ®Google Scholar
• Ponti D, Zaffaroni N, Capelli C, Daidone MG.Breast cancer stem cells: An overview. Eur J Cancer 2006;42:1219–1224.
   PubMed Web of Science ®Google Scholar
• Dalerba P, Cho RW, Clarke M.Cancer stem cells: Models and concepts. Annu Rev Med 2007;58:267–284.
   PubMed Web of Science ®Google Scholar
• Fillmore CM, Kuperwasser C.Human breast cancer cell lines contain stem-like cells that self-renew, give rise to phenotypically diverse progeny and survive chemotherapy. Br Cancer Res 2008;10:1–13.
   Web of Science ®Google Scholar
• Villadsen R, Fridriksdottir AJ, Rønnov-Jessen L, Gudjonsson T, Rank F, LaBarge MA, Bissell MJ, Petersen OW.Evidence for a stem cell hierarchy in the adult human breast. J Cell Biol 2007;177:87–101.
   PubMed Web of Science ®Google Scholar
• Ginestier C, Hur MH, Charafe-Jauffret E, Monville F, Dutcher J, Brown M, Jacquemier J, Viens P, Kleer CG, Liu S, Schott A, Hayes D, Birnbaum D, Wicha MS, Dontu G.ALDHI is a marker of normal and malignant human mammary stem cells and a predictor of poor clinical outcome. Cell Stem Cell 2007;1:555–567.
   PubMed Web of Science ®Google Scholar
• Yun K, Tennent B.Cancer stem cells. Drug discovery today: Disease Models 2008;4(2):47–51.
   Google Scholar
• Kakarala M, Wicha MS.Implications of the cancer stem-cell hypothesis for breast cancer prevention and treatment. J Clin Oncol 2008;26:2813–2820.
   PubMed Web of Science ®Google Scholar
• Hwang-Verslues WW, Chang KJ, Lee EY, Lee WH.Breast cancer stem cells and tumor suppressor genes. J Formos Med Assoc 2008;107(10):751–766.
   PubMed Web of Science ®Google Scholar
• O'Brien CS, Howell SJ, Farnie G, Clarke RB.Resistance to endocrine therapy: Are breast cancer stem cells the culprits? J Mammary Gland Biol Neoplasia 2009;14:45–54.
   PubMed Web of Science ®Google Scholar
• Muehlberg FL, Song YH, Krohn A, Pinilla SP, Droll LH, Leng X, Seidensticker M, Ricke J, Altman AM, Devarajan E, Liu W, Arlinghaus RB, Alt EU.Tissue-resident stem cells promote breast cancer growth and metastasis. Carcinogenesis 2009;30(4):589–597.
   PubMed Web of Science ®Google Scholar
• Charafe-Jauffret E, Ginestier C, Iovino F, Wicinski J, Cervera N, Finetti P, Hur MH, Diebel ME, Monville F, Dutcher J, Brown M, Viens P, Xerri L, Bertucci F, Stassi G, Dontu G, Birnbaum D, Wicha MS.Breast cancer cell lines contain functional cancer stem cells with metastatic capacity and a distinct molecular signal. Cancer Res 2009;69(4):1302–1313.
   PubMed Web of Science ®Google Scholar
• Tanei T, Morimoto K, Shimazu K, Seung JK, Tanji Y, Taguchi T, Tamaki Y, Noguchi S.Association of breast cancer stem cells identified by aldehyde dehydrogenase 1 expression with resistance to sequential paclitaxel and epirubicin-based chemotherapy. Clin Cancer Res 2009;15 (12):4234–4241.
   PubMed Web of Science ®Google Scholar
• Horwitz KB, Dye WW, Harrell JC, Kabos P, Sartorius CA.Rare steroid receptor-negative basal-like tumorigenic cells in luminal subtype human breast cancer xenografts. Proc Natl Acad Sci USA 2008;105:5774–5779.
   PubMed Web of Science ®Google Scholar
• Horwitz KB, Sartorius CA.Progestins in hormone replacement therapies reactivate cancer stem cells in women with pre-existing breast cancers: a hypothesis. J Clin Endocrinol Metab 2008;93:3295–3298.
   PubMed Web of Science ®Google Scholar
• Horwitz KB.The year in Basic Science: Update of estrogen plus progestin therapy for menopausal hormone replacement implicating stem cells in the increased breast cancer risk. Mole Endocrinol 2008;22:2743–2750.
   PubMedGoogle Scholar
• Licznerska BE, Wegman PP, Nordenskjold B, Wingren S.In situ levels of estrogen producing enzymes and its prognostic significance in postmenopausal breast cancer patients. Br Cancer Treat 2008;112:15–23.
   PubMed Web of Science ®Google Scholar
• Pasqualini JR, Chetrite GS.Recent insight on the control of enzymes involved in estrogen formation and transformation in human breast cancer. J Steroid Biochem Mol Biol 2005;93:221–236.
   PubMed Web of Science ®Google Scholar
• Aka JA, Mazumdar M, Lin SX.Reductive 17β-hydroxysteroid dehydrogenases in the sulfatase pathway: Critical in the cell proliferation of breast cancer. Mol Cell Endocrinol 2009;301:183–190.
   PubMed Web of Science ®Google Scholar
• Stute P, Gotte M, Kiesel L.Differential effect of hormone therapy on E1S-sulfatase activity in non–malignant and cancerous breast cells in vitro. Br Cancer Res Treat 2008;108:363-374.
   PubMed Web of Science ®Google Scholar
• Suzuki T, Miki Y, Akahira JI, Moriya T, Ohuchi N, Sasano H.Aromatase in human breast carcinoma as a key regulator of intratumoral sex steroid concentrations. Endo J 2008;55(3):455–463.
   PubMed Web of Science ®Google Scholar
• Wren BG.Do female sex hormones initiate breast cancer? A review of the evidence. Climacteric 2004;7:120–128.
   PubMed Web of Science ®Google Scholar
• Suzuki T, Miki Y, Nakamura Y, Moriya T, Ito K, Ohuchi N, Sasano H.Sex steroid-producing enzymes in human breast cancer. Endocr Relat Cancer 2005;12:701–720.
   PubMed Web of Science ®Google Scholar
• Clarke RB.Ovarian steroids and the human breast: Regulation of stem cells and cell proliferation. Maturitas 2006;54:327–333.
   PubMed Web of Science ®Google Scholar
• Clarke RB.Human breast cell proliferation and its relationship to steroid receptor expression. Climacteric 2004;7:129–137.
   PubMed Web of Science ®Google Scholar
• Clarke RB, Spence K, Anderson E, Howell A, Okano H, Potten CS.A putative human breast stem cell population is enriched for steroid receptor-positive cells. Dev Biol 2005;277:443–456.
   PubMed Web of Science ®Google Scholar
• Mousa NA, Casper RF.Menopausal estrogen deprivation activates steroid sensitive stem cells (3SC) and local estrogen biosynthesis: A model for breast cancer development. Biosc Hypoth 2009;2:252–256.
   Google Scholar