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Impact of recent parity on histopathological tumor features and breast cancer outcome in premenopausal Japanese women

  • Epidemiology
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Abstract

Although previous studies have reported that onset at young age is associated with poor prognosis in breast cancer, the correlation between reproductive factors, breast cancer characteristics, and prognosis remains unclear. Five hundred and twenty-six premenopausal young women diagnosed with primary invasive breast cancer between January 2000 and December 2007 were included in this study. Patients were classified into four groups according to their reproductive history: women who gave birth within the previous 2 years (group A), women who gave birth between 3 and 5 years previously (group B), women who gave birth more than 5 years previously (group C), and nulliparous women (group N). The correlation between the time since last childbirth to diagnosis, histopathological tumor features, and breast cancer prognosis was evaluated. Breast cancer patients who had given birth more recently had more advanced stage tumors; larger sized tumors; a higher rate of axillary lymph node metastases; a higher histological tumor grade; and increased progesterone receptor (PgR)−, HER2+, and triple negative tumors than patients who had given birth less recently or not at all. Group A patients had significantly shorter survival times than patients in both groups C and N (log rank test; p < 0.001). After adjusting for tumor characteristics, the hazard ratio for death in group A was 2.19 compared with group N (p = 0.036), and the adjusted hazard ratio restricted to patients in group A with hormone-receptor-positive, and HER2− tumors was 3.07 (p = 0.011). Young breast cancer patients who had given birth more recently had tumors with more aggressive features and worse prognoses compared with patients who had given birth less recently or were nulliparous.

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References

  1. Chung M, Chang HR, Bland KI, Wanebo HJ (1996) Younger women with breast carcinoma have a poorer prognosis than older women. Cancer 77(1):97–103. doi:10.1002/(SICI)1097-0142(19960101)77:1<97:AID-CNCR16>3.0.CO;2-3

    Article  PubMed  CAS  Google Scholar 

  2. de la Rochefordiere A, Asselain B, Campana F, Scholl SM, Fenton J, Vilcoq JR, Durand JC, Pouillart P, Magdelenat H, Fourquet A (1993) Age as prognostic factor in premenopausal breast carcinoma. Lancet 341(8852):1039–1043. doi:10.1016/0140-6736(93)92407-K

    Article  PubMed  Google Scholar 

  3. Fredholm H, Eaker S, Frisell J, Holmberg L, Fredriksson I, Lindman H (2009) Breast cancer in young women: poor survival despite intensive treatment. PLoS ONE 4(11):e7695. doi:10.1371/journal.pone.0007695

    Article  PubMed  Google Scholar 

  4. Peng R, Wang S, Shi Y, Liu D, Teng X, Qin T, Zeng Y, Yuan Z (2011) Patients 35 years old or younger with operable breast cancer are more at risk for relapse and survival: a retrospective matched case-control study. Breast. doi:10.1016/j.breast.2011.07.012

    PubMed  Google Scholar 

  5. Yoshida M, Shimizu C, Fukutomi T, Tsuda H, Kinoshita T, Akashi-Tanaka S, Ando M, Hojo T, Fujiwara Y (2011) Prognostic factors in young Japanese women with breast cancer: prognostic value of age at diagnosis. Jpn J Clin Oncol 41(2):180–189. doi:10.1093/jjco/hyq191

    Article  PubMed  Google Scholar 

  6. Middleton LP, Amin M, Gwyn K, Theriault R, Sahin A (2003) Breast carcinoma in pregnant women: assessment of clinicopathologic and immunohistochemical features. Cancer 98(5):1055–1060. doi:10.1002/cncr.11614

    Article  PubMed  Google Scholar 

  7. Ma H, Bernstein L, Pike MC, Ursin G (2006) Reproductive factors and breast cancer risk according to joint estrogen and progesterone receptor status: a meta-analysis of epidemiological studies. Breast Cancer Res 8(4):R43. doi:10.1186/bcr1525

    Article  PubMed  Google Scholar 

  8. Xing P, Li J, Jin F (2010) A case–control study of reproductive factors associated with subtypes of breast cancer in Northeast China. Med Oncol 27(3):926–931. doi:10.1007/s12032-009-9308-7

    Article  PubMed  Google Scholar 

  9. Suzuki R, Rylander-Rudqvist T, Ye W, Saji S, Wolk A (2006) Body weight and postmenopausal breast cancer risk defined by estrogen and progesterone receptor status among Swedish women: a prospective cohort study. Int J Cancer 119(7):1683–1689. doi:10.1002/ijc.22034

    Article  PubMed  CAS  Google Scholar 

  10. Iwasaki M, Otani T, Inoue M, Sasazuki S, Tsugane S (2007) Body size and risk for breast cancer in relation to estrogen and progesterone receptor status in Japan. Ann Epidemiol 17(4):304–312. doi:10.1016/j.annepidem.2006.09.003

    Article  PubMed  Google Scholar 

  11. Canchola AJ, Anton-Culver H, Bernstein L, Clarke CA, Henderson K, Ma H, Ursin G, Horn-Ross PL (2012) Body size and the risk of postmenopausal breast cancer subtypes in the California Teachers Study cohort. Cancer Causes Control. doi:10.1007/s10552-012-9897-x

    PubMed  Google Scholar 

  12. Zakhartseva LM, Gorovenko NG, Podolskaya SV, Anikusko NF, Lobanova OE, Pekur KA, Kropelnytskyi VA, Shurygina OV (2009) Breast cancer immunohistochemical features in young women with BRCA 1/2 mutations. Exp Oncol 31(3):174–178

    PubMed  CAS  Google Scholar 

  13. Southey MC, Ramus SJ, Dowty JG, Smith LD, Tesoriero AA, Wong EE, Dite GS, Jenkins MA, Byrnes GB, Winship I, Phillips KA, Giles GG, Hopper JL (2011) Morphological predictors of BRCA1 germline mutations in young women with breast cancer. Br J Cancer 104(6):903–909. doi:10.1038/bjc.2011.41

    Article  PubMed  CAS  Google Scholar 

  14. Rennert G, Bisland-Naggan S, Barnett-Griness O, Bar-Joseph N, Zhang S, Rennert HS, Narod SA (2007) Clinical outcomes of breast cancer in carriers of BRCA1 and BRCA2 mutations. N Engl J Med 357(2):115–123. doi:10.1056/NEJMoa070608

    Article  PubMed  CAS  Google Scholar 

  15. Chen XS, Ma CD, Wu JY, Yang WT, Lu HF, Wu J, Lu JS, Shao ZM, Shen ZZ, Shen KW (2010) Molecular subtype approximated by quantitative estrogen receptor, progesterone receptor and Her2 can predict the prognosis of breast cancer. Tumori 96(1):103–110

    PubMed  Google Scholar 

  16. van der Hage JA, Mieog JS, van de Velde CJ, Putter H, Bartelink H, van de Vijver MJ (2011) Impact of established prognostic factors and molecular subtype in very young breast cancer patients: pooled analysis of four EORTC randomized controlled trials. Breast Cancer Res 13(3):R68. doi:10.1186/bcr2908

    Article  PubMed  Google Scholar 

  17. Blows FM, Driver KE, Schmidt MK, Broeks A, van Leeuwen FE, Wesseling J, Cheang MC, Gelmon K, Nielsen TO, Blomqvist C, Heikkila P, Heikkinen T, Nevanlinna H, Akslen LA, Begin LR, Foulkes WD, Couch FJ, Wang X, Cafourek V, Olson JE, Baglietto L, Giles GG, Severi G, McLean CA, Southey MC, Rakha E, Green AR, Ellis IO, Sherman ME, Lissowska J, Anderson WF, Cox A, Cross SS, Reed MW, Provenzano E, Dawson SJ, Dunning AM, Humphreys M, Easton DF, Garcia-Closas M, Caldas C, Pharoah PD, Huntsman D (2010) Subtyping of breast cancer by immunohistochemistry to investigate a relationship between subtype and short and long term survival: a collaborative analysis of data for 10,159 cases from 12 studies. PLoS Med 7(5):e1000279. doi:10.1371/journal.pmed.1000279

    Article  PubMed  Google Scholar 

  18. Bladstrom A, Anderson H, Olsson H (2003) Worse survival in breast cancer among women with recent childbirth: results from a Swedish population-based register study. Clin Breast Cancer 4(4):280–285

    Article  PubMed  Google Scholar 

  19. Rosenberg L, Thalib L, Adami HO, Hall P (2004) Childbirth and breast cancer prognosis. Int J Cancer 111(5):772–776. doi:10.1002/ijc.20323

    Article  PubMed  CAS  Google Scholar 

  20. Trivers KF, Gammon MD, Abrahamson PE, Lund MJ, Flagg EW, Kaufman JS, Moorman PG, Cai J, Olshan AF, Porter PL, Brinton LA, Eley JW, Coates RJ (2007) Association between reproductive factors and breast cancer survival in younger women. Breast Cancer Res Treat 103(1):93–102. doi:10.1007/s10549-006-9346-1

    Article  PubMed  Google Scholar 

  21. Dodds L, Fell DB, Joseph KS, Dewar R, Scott H, Platt R, Aronson KJ (2008) Relationship of time since childbirth and other pregnancy factors to premenopausal breast cancer prognosis. Obstet Gynecol 111(5):1167–1173. doi:10.1097/AOG.0b013e31816fd778

    Article  PubMed  Google Scholar 

  22. Johansson AL, Andersson TM, Hsieh CC, Cnattingius S, Lambe M (2011) Increased mortality in women with breast cancer detected during pregnancy and different periods postpartum. Cancer Epidemiol Biomark Prev 20(9):1865–1872. doi:10.1158/1055-9965.EPI-11-0515

    Article  Google Scholar 

  23. Daling JR, Malone KE, Doody DR, Anderson BO, Porter PL (2002) The relation of reproductive factors to mortality from breast cancer. Cancer Epidemiol Biomark Prev 11(3):235–241

    Google Scholar 

  24. Phillips KA, Milne RL, Friedlander ML, Jenkins MA, McCredie MR, Giles GG, Hopper JL (2004) Prognosis of premenopausal breast cancer and childbirth prior to diagnosis. J Clin Oncol 22(4):699–705. doi:10.1200/JCO.2004.07.062

    Article  PubMed  Google Scholar 

  25. Kroman N, Wohlfahrt J, Andersen KW, Mouridsen HT, Westergaard T, Melbye M (1997) Time since childbirth and prognosis in primary breast cancer: population based study. BMJ 315(7112):851–855

    Article  PubMed  CAS  Google Scholar 

  26. Olson SH, Zauber AG, Tang J, Harlap S (1998) Relation of time since last birth and parity to survival of young women with breast cancer. Epidemiology 9(6):669–671

    Article  PubMed  CAS  Google Scholar 

  27. Beadle BM, Woodward WA, Middleton LP, Tereffe W, Strom EA, Litton JK, Meric-Bernstam F, Theriault RL, Buchholz TA, Perkins GH (2009) The impact of pregnancy on breast cancer outcomes in women < or = 35 years. Cancer 115(6):1174–1184. doi:10.1002/cncr.24165

    Article  PubMed  Google Scholar 

  28. Butt S, Borgquist S, Anagnostaki L, Landberg G, Manjer J (2009) Parity and age at first childbirth in relation to the risk of different breast cancer subgroups. Int J Cancer 125(8):1926–1934. doi:10.1002/ijc.24494

    Article  PubMed  CAS  Google Scholar 

  29. Loibl S, Jackisch C, Gade S, Untch M, Paepke S, Kuemmel S, Schneeweiss A, Jackisch C, Huober J, Hilfrich J, Hanusch C, Gerber B, Eidtmann H, Denkert C, Costa S-D, Blohmer J-U, Nekljudova V, Mehta K, Minckwitz G (2012) Neoadjuvant chemotherapy in the very young 35 years of age or younger. Cancer Res 72(24 Suppl):Abstract no S3-1

  30. Collins LC, Marotti JD, Gelber S, Cole K, Ruddy K, Kereakoglow S, Brachtel EF, Schapira L, Come SE, Winer EP, Partridge AH (2012) Pathologic features and molecular phenotype by patient age in a large cohort of young women with breast cancer. Breast Cancer Res Treat 131(3):1061–1066. doi:10.1007/s10549-011-1872-9

    Article  PubMed  CAS  Google Scholar 

  31. Whiteman MK, Hillis SD, Curtis KM, McDonald JA, Wingo PA, Marchbanks PA (2004) Reproductive history and mortality after breast cancer diagnosis. Obstet Gynecol 104(1):146–154. doi:10.1097/01.AOG.0000128173.01611.ff

    Article  PubMed  Google Scholar 

  32. Murphy CG, Mallam D, Stein S, Patil S, Howard J, Sklarin N, Hudis CA, Gemignani ML, Seidman AD (2011) Current or recent pregnancy is associated with adverse pathologic features but not impaired survival in early breast cancer. Cancer. doi:10.1002/cncr.26654

    Google Scholar 

  33. Russo J, Moral R, Balogh GA, Mailo D, Russo IH (2005) The protective role of pregnancy in breast cancer. Breast Cancer Res 7(3):131–142. doi:10.1186/bcr1029

    Article  PubMed  Google Scholar 

  34. Liu Q, Wuu J, Lambe M, Hsieh SF, Ekbom A, Hsieh CC (2002) Transient increase in breast cancer risk after giving birth: postpartum period with the highest risk (Sweden). Cancer Causes Control 13(4):299–305

    Article  PubMed  Google Scholar 

  35. Schedin P (2006) Pregnancy-associated breast cancer and metastasis. Nat Rev Cancer 6(4):281–291. doi:10.1038/nrc1839

    Article  PubMed  CAS  Google Scholar 

  36. Grubbs CJ, Hill DL, McDonough KC, Peckham JC (1983) N-nitroso-N-methylurea-induced mammary carcinogenesis: effect of pregnancy on preneoplastic cells. J Natl Cancer Inst 71(3):625–628

    PubMed  CAS  Google Scholar 

  37. Henderson BE, Ross R, Bernstein L (1988) Estrogens as a cause of human cancer: the Richard and Hinda Rosenthal Foundation award lecture. Cancer Res 48(2):246–253

    PubMed  CAS  Google Scholar 

  38. Rossouw JE, Anderson GL, Prentice RL, LaCroix AZ, Kooperberg C, Stefanick ML, Jackson RD, Beresford SA, Howard BV, Johnson KC, Kotchen JM, Ockene J (2002) Risks and benefits of estrogen plus progestin in healthy postmenopausal women: principal results From the Women’s Health Initiative randomized controlled trial. JAMA 288(3):321–333

    Article  PubMed  CAS  Google Scholar 

  39. Hankinson SE, Colditz GA, Willett WC (2004) Towards an integrated model for breast cancer etiology: the lifelong interplay of genes, lifestyle, and hormones. Breast Cancer Res 6(5):213–218. doi:10.1186/bcr921

    Article  PubMed  CAS  Google Scholar 

  40. Kleinberg DL, Wood TL, Furth PA, Lee AV (2009) Growth hormone and insulin-like growth factor-I in the transition from normal mammary development to preneoplastic mammary lesions. Endocr Rev 30(1):51–74. doi:10.1210/er.2008-0022

    Article  PubMed  CAS  Google Scholar 

  41. Russo J, Balogh GA, Russo IH (2008) Full-term pregnancy induces a specific genomic signature in the human breast. Cancer Epidemiol Biomarkers Prev 17(1):51–66. doi:10.1158/1055-9965.EPI-07-0678

    Article  PubMed  CAS  Google Scholar 

  42. Asztalos S, Gann PH, Hayes MK, Nonn L, Beam CA, Dai Y, Wiley EL, Tonetti DA (2010) Gene expression patterns in the human breast after pregnancy. Cancer Prev Res 3(3):301–311. doi:10.1158/1940-6207.CAPR-09-0069

    Article  CAS  Google Scholar 

  43. Belitskaya-Levy I, Zeleniuch-Jacquotte A, Russo J, Russo IH, Bordas P, Ahman J, Afanasyeva Y, Johansson R, Lenner P, Li X, de Cicco RL, Peri S, Ross E, Russo PA, Santucci-Pereira J, Sheriff FS, Slifker M, Hallmans G, Toniolo P, Arslan AA (2011) Characterization of a genomic signature of pregnancy identified in the breast. Cancer Prev Res 4(9):1457–1464. doi:10.1158/1940-6207.CAPR-11-0021

    Article  Google Scholar 

  44. Gonzalez-Suarez E, Jacob AP, Jones J, Miller R, Roudier-Meyer MP, Erwert R, Pinkas J, Branstetter D, Dougall WC (2010) RANK ligand mediates progestin-induced mammary epithelial proliferation and carcinogenesis. Nature 468(7320):103–107. doi:10.1038/nature09495

    Article  PubMed  CAS  Google Scholar 

  45. Schramek D, Leibbrandt A, Sigl V, Kenner L, Pospisilik JA, Lee HJ, Hanada R, Joshi PA, Aliprantis A, Glimcher L, Pasparakis M, Khokha R, Ormandy CJ, Widschwendter M, Schett G, Penninger JM (2010) Osteoclast differentiation factor RANKL controls development of progestin-driven mammary cancer. Nature 468(7320):98–102. doi:10.1038/nature09387

    Article  PubMed  CAS  Google Scholar 

  46. Borges VF, Callihan E, Jindal S, Lyons T, Manthey E, Gao D, Schedin PJ (2011) The post-partum diagnosis of pregnancy associated breast cancer confers an increased risk for metastasis without increased incidence of poorer prognosis biologic subtype. Cancer Res 71(24 Suppl):Abstract no P2-01-04. doi:10.1158/0008-5472.SABCS11-P2-01-04

  47. Sugano K, Nakamura S, Ando J, Takayama S, Kamata H, Sekiguchi I, Ubukata M, Kodama T, Arai M, Kasumi F, Hirai Y, Ikeda T, Jinno H, Kitajima M, Aoki D, Hirasawa A, Takeda Y, Yazaki K, Fukutomi T, Kinoshita T, Tsunematsu R, Yoshida T, Izumi M, Umezawa S, Yagata H, Komatsu H, Arimori N, Matoba N, Gondo N, Yokoyama S, Miki Y (2008) Cross-sectional analysis of germline BRCA1 and BRCA2 mutations in Japanese patients suspected to have hereditary breast/ovarian cancer. Cancer Sci 99(10):1967–1976. doi:10.1111/j.1349-7006.2008.00944.x

    Article  PubMed  CAS  Google Scholar 

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Acknowledgments

This study was supported by the “Yomei 1-kagetsu no hanayome” Memorial Grant of the Foundation for Promotion of Cancer Research and Grant-in-aid for Cancer Research (H21-021) from the Ministry of Health, Labour and Welfare of Japan.

Conflict of interest

The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Division of Breast and Medical Oncology, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo, 104-0045, Japan

    Akiko Kawano Nagatsuma, Chikako Shimizu & Yasuhiro Fujiwara

  2. Division of Pathology and Clinical Laboratories, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo, 104-0045, Japan

    Hitoshi Tsuda

  3. Department of Clinical Medicine (Biostatistics & Pharmaceutical Medicine), School of Pharmacy, Kitasato University, 5-9-1, Shirokane, Minato-ku, Tokyo, 108-8641, Japan

    Fumiaki Takahashi & Masahiro Takeuchi

  4. Department of Target Therapy Oncology, Kyoto University Graduate School of Medicine, 54 Shogoin Kawahara-cho, Sakyo-ku, Kyoto, 606-8507, Japan

    Shigehira Saji

  5. Oncogene Research Unit/Cancer Prevention Unit, Tochigi Cancer Research Institute, 4-9-13, Yonan, Utsunomiya-city, Tochigi, 320-0834, Japan

    Kokichi Sugano

  6. Department of Medical Oncology, Jichi Medical University Hospital, 3311-1, Yakushiji, Shimotsuke-city, Tochigi, 329-0498, Japan

    Akiko Kawano Nagatsuma & Hirofumi Fujii

  7. Breast Surgery Division, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo, 104-0045, Japan

    Takashi Hojo

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  1. Akiko Kawano Nagatsuma
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  2. Chikako Shimizu
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  3. Fumiaki Takahashi
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  8. Masahiro Takeuchi
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  9. Hirofumi Fujii
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  10. Yasuhiro Fujiwara
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Correspondence to Chikako Shimizu.

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Nagatsuma, A.K., Shimizu, C., Takahashi, F. et al. Impact of recent parity on histopathological tumor features and breast cancer outcome in premenopausal Japanese women. Breast Cancer Res Treat 138, 941–950 (2013). https://doi.org/10.1007/s10549-013-2507-0

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