Cancer Causes & Control

, Volume 24, Issue 11, pp 1911–1923 | Cite as

Puerperal mastitis: a reproductive event of importance affecting anti-mucin antibody levels and ovarian cancer risk

  • Daniel W. Cramer
  • Kristina Williams
  • Allison F. Vitonis
  • Hidemi S. Yamamoto
  • Alison Stuebe
  • William R. Welch
  • Linda Titus
  • Raina N. Fichorova
Original paper



Test the hypothesis that puerperal mastitis may alter immunity related to the mucin (MUC) family of glycoproteins and lower risk of ovarian cancer.


In two case–control studies conducted in New England between 1998 and 2008, we examined the association between self-reported mastitis and ovarian cancer in 1,483 women with epithelial ovarian cancer and 1,578 controls. IgG1 antibodies against (MUC1) CA15.3 and (MUC16) CA125 were measured using electrochemiluminescence assays in a subset of controls (n = 200). Preoperative CA125 was recorded in 649 cases. The association between ovarian cancer and mastitis was assessed using unconditional logistic regression to calculate adjusted odds ratios, OR, and 95 % confidence intervals (CI). Associations between mastitis and anti-CA15.3 and anti-CA125 antibodies and preoperative CA125 levels were evaluated using adjusted linear regression models.


Prior mastitis was associated with a significantly lower risk of ovarian cancer: OR (and 95 % CI) of 0.67 (0.48, 0.94) adjusted for parity, breastfeeding, and other potential confounders. The association was strongest with 2 or more episodes of mastitis, and risk declined progressively with increasing number of children and episodes of mastitis. Among controls, prior mastitis was associated with significantly higher anti-CA15.3 and anti-CA125 antibody levels and, among cases, with significantly lower preoperative CA125 levels.


Puerperal mastitis may produce long-lasting anti-mucin antibodies that may lower the risk of ovarian cancer, plausibly through enhanced immune surveillance. Studying immune reactions related to MUC1 and MUC16 in the 10–20 % of breastfeeding women who develop mastitis may suggest ways to duplicate its effects through vaccines based on both antigens.


CA125 CA15.3 Ovarian cancer Puerperal mastitis 



We acknowledge Professor Olivera J. Finn for her support of our prior studies of mucin immunity and ovarian cancer and her thoughtful input on this manuscript. We thank John R. McKolanis for his technical advice on the anti-mucin assays, and Hassan Y. Dawood, B.S. for performing the anti-CA125 and anti CA15.3 immunoassays in Dr. Fichorova’s laboratory. This work is dedicated to the memory of Katherine Astrove in recognition of her husband’s long-term support of research on ovarian cancer at the Brigham and Women’s Hospital. This research was supported by the National Institutes of Health (Grant numbers. R01CA123170, R01CA54419, and P50CA105009 to DWC) and donations from Mr. Edgar Astrove.

Conflict of interest

Daniel W. Cramer is a plantiff’s witness in litigation related to ovarian cancer. The remaining authors declare that they have no conflict of interest.


  1. 1.
    Howlader N, Noone AM, Krapcho M, Neyman N, Aminou R, et al (2012) SEER cancer statistics review, 1975–2009 (vintage 2009 populations). National Cancer Institute, Bethesda., based on November 2011 SEER data submission, posted to the SEER web site
  2. 2.
    Casagrande JT, Louie EW, Pike MC, Roy S, Ross RK et al (1979) “Incessant ovulation” and ovarian cancer. Lancet 2:170–173PubMedCrossRefGoogle Scholar
  3. 3.
    Hankinson SE, Hunter DJ, Colditz GA, Willett WC, Stampfer MJ et al (1993) Tubal ligation, hysterectomy, and risk of ovarian cancer. A prospective study. JAMA 270:2813–2818PubMedCrossRefGoogle Scholar
  4. 4.
    Langseth H, Hankinson SE, Siemiatycki J, Weiderpass E (2008) Perineal use of talc and risk of ovarian cancer. J Epidemiol Commun Health 62:358–360CrossRefGoogle Scholar
  5. 5.
    Pearce CL, Templeman C, Rossing MA, Lee A, Near AM et al (2012) Association between endometriosis and risk of histological subtypes of ovarian cancer: a pooled analysis of case-control studies. Lancet Oncol 13:385–394PubMedCrossRefGoogle Scholar
  6. 6.
    Cramer DW, Titus-Ernstoff L, McKolanis JR, Welch WR, Vitonis AF et al (2005) Conditions associated with antibodies against the tumor-associated antigen MUC1 and their relationship to risk for ovarian cancer. Cancer Epidemiol Biomarkers Prev 14:1125–1131PubMedCrossRefGoogle Scholar
  7. 7.
    Pinheiro SP, Hankinson SE, Tworoger SS, Rosner BA, McKolanis JR et al (2010) Anti-MUC1 antibodies and ovarian cancer risk: prospective data from the Nurses’ Health Studies. Cancer Epidemiol Biomarkers Prev 19:1595–1601PubMedCrossRefGoogle Scholar
  8. 8.
    Cramer DW, Vitonis AF, Pinheiro SP, McKolanis JR, Fichorova RN et al (2010) Mumps and ovarian cancer: modern interpretation of an historic association. Cancer Causes Control 21:1193–1201PubMedCrossRefGoogle Scholar
  9. 9.
    Vitonis AF, Titus-Ernstoff L, Cramer DW (2011) Assessing ovarian cancer risk when considering elective oophorectomy at the time of hysterectomy. Obstet Gynecol 117:1042–1050PubMedCrossRefGoogle Scholar
  10. 10.
    Cramer DW, Vitonis AF, Welch WR, Terry KL, Goodman A et al (2010) Correlates of the preoperative level of CA125 at presentation of ovarian cancer. Gynecol Oncol 119:462–468PubMedCrossRefGoogle Scholar
  11. 11.
    Fichorova RN, Richardson-Harman N, Alfano M, Belec L, Carbonneil C, et al (2008) Biological and technical variables affecting immunoassay recovery of cytokines from human serum and simulated vaginal fluid: a multicenter study. Anal Chem 80:4741–4751 Google Scholar
  12. 12.
    Rosner B, Cook N, Portman R, Daniels S, Falkner B (2008) Determination of blood pressure percentiles in normal-weight children: some methodological issues. Am J Epidemiol 167:653–666PubMedCrossRefGoogle Scholar
  13. 13.
    Foxman B, D’Arcy H, Gillespie B, Bobo JK, Schwartz K (2002) Lactation mastitis: occurrence and medical management among 946 breastfeeding women in the United States. Am J Epidemiol 155:103–114PubMedCrossRefGoogle Scholar
  14. 14.
    Jonsson S, Pulkkinen MO (1994) Mastitis today: incidence, prevention and treatment. Ann Chir Gynaecol Suppl 208:84–87PubMedGoogle Scholar
  15. 15.
    Olsen CM, Nagle CM, Whiteman DC, Ness R, Pearce CL et al (2013) Obesity and risk of ovarian cancer subtypes: evidence from the ovarian cancer association consortium. Endocr Relat Cancer 20:251–262PubMedCrossRefGoogle Scholar
  16. 16.
    Jordan SJ, Cushing-Haugen KL, Wicklund KG, Doherty JA, Rossing MA (2012) Breast-feeding and risk of epithelial ovarian cancer. Cancer Causes Control 23:919–927PubMedCrossRefGoogle Scholar
  17. 17.
    Shore RE, Hildreth N, Woodard E, Dvoretsky P, Hempelmann L et al (1986) Breast cancer among women given X-ray therapy for acute postpartum mastitis. J Natl Cancer Inst 77:689–696PubMedGoogle Scholar
  18. 18.
    Lambe M, Johansson AL, Altman D, Eloranta S (2009) Mastitis and the risk of breast cancer. Epidemiology 20:747–751PubMedCrossRefGoogle Scholar
  19. 19.
    Stafford I, Hernandez J, Laibl V, Sheffield J, Roberts S et al (2008) Community-acquired methicillin-resistant Staphylococcus aureus among patients with puerperal mastitis requiring hospitalization. Obstet Gynecol 112:533–537PubMedCrossRefGoogle Scholar
  20. 20.
    Peat N, Gendler SJ, Lalani N, Duhig T, Taylor-Papadimitriou J (1992) Tissue-specific expression of a human polymorphic epithelial mucin (MUC1) in transgenic mice. Cancer Res 52:1954–1960PubMedGoogle Scholar
  21. 21.
    Croce MV, Isla-Larrain MT, Capafons A, Price MR, Segal-Eiras A (2001) Humoral immune response induced by the protein core of MUC1 mucin in pregnant and healthy women. Breast Cancer Res Treat 69:1–11PubMedCrossRefGoogle Scholar
  22. 22.
    Jerome KR, Kirk AD, Pecher G, Ferguson WW, Finn OJ (1997) A survivor of breast cancer with immunity to MUC-1 mucin, and lactational mastitis. Cancer Immunol Immunother 43:355–360PubMedCrossRefGoogle Scholar
  23. 23.
    Gunther J, Petzl W, Zerbe H, Schuberth HJ, Koczan D et al (2012) Lipopolysaccharide priming enhances expression of effectors of immune defence while decreasing expression of pro-inflammatory cytokines in mammary epithelia cells from cows. BMC Genomics 13:17PubMedCrossRefGoogle Scholar
  24. 24.
    Hardardottir H, Parmley TH 2nd, Quirk JG Jr, Sanders MM, Miller FC et al (1990) Distribution of CA 125 in embryonic tissues and adult derivatives of the fetal periderm. Am J Obstet Gynecol 163:1925–1931PubMedCrossRefGoogle Scholar
  25. 25.
    Han SN, Lotgerink A, Gziri MM, Van Calsteren K, Hanssens M et al (2012) Physiologic variations of serum tumor markers in gynecological malignancies during pregnancy: a systematic review. BMC Med 10:86PubMedCrossRefGoogle Scholar
  26. 26.
    Sarandakou A, Protonotariou E, Rizos D (2007) Tumor markers in biological fluids associated with pregnancy. Crit Rev Clin Lab Sci 44:151–178PubMedCrossRefGoogle Scholar
  27. 27.
    Hammer JF, Morton JM, Kerrisk KL (2012) Quarter-milking-, quarter-, udder- and lactation-level risk factors and indicators for clinical mastitis during lactation in pasture-fed dairy cows managed in an automatic milking system. Aust Vet J 90:167–174PubMedCrossRefGoogle Scholar
  28. 28.
    Ryan AS, Wenjun Z, Acosta A (2002) Breastfeeding continues to increase into the new millennium. Pediatrics 110:1103–1109PubMedCrossRefGoogle Scholar
  29. 29.
    Sjovall K, Nilsson B, Einhorn N (2002) The significance of serum CA 125 elevation in malignant and nonmalignant diseases. Gynecol Oncol 85:175–178PubMedCrossRefGoogle Scholar
  30. 30.
    Yonezawa S, Higashi M, Yamada N, Yokoyama S, Kitamoto S et al (2011) Mucins in human neoplasms: clinical pathology, gene expression and diagnostic application. Pathol Int 61:697–716PubMedCrossRefGoogle Scholar
  31. 31.
    von Mensdorff-Pouilly S, Verstraeten AA, Kenemans P, Snijdewint FG, Kok A et al (2000) Survival in early breast cancer patients is favorably influenced by a natural humoral immune response to polymorphic epithelial mucin. J Clin Oncol 18:574–583Google Scholar
  32. 32.
    Gourevitch MM, von Mensdorff-Pouilly S, Litvinov SV, Kenemans P, van Kamp GJ et al (1995) Polymorphic epithelial mucin (MUC-1)-containing circulating immune complexes in carcinoma patients. Br J Cancer 72:934–938PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media Dordrecht 2013

Authors and Affiliations

  • Daniel W. Cramer
    • 1
    • 2
  • Kristina Williams
    • 2
  • Allison F. Vitonis
    • 1
  • Hidemi S. Yamamoto
    • 3
  • Alison Stuebe
    • 4
  • William R. Welch
    • 5
  • Linda Titus
    • 6
    • 7
  • Raina N. Fichorova
    • 3
    • 2
  1. 1.Department of Obstetrics, Gynecology and Reproductive Biology, Obstetrics and Gynecology Epidemiology CenterBrigham and Women’s HospitalBostonUSA
  2. 2.Harvard Medical SchoolBostonUSA
  3. 3.Laboratory of Genital Tract Biology, Department of Obstetrics, Gynecology and Reproductive BiologyBrigham and Women’s HospitalBostonUSA
  4. 4.Division of Maternal-Fetal MedicineUniversity of North Carolina School of MedicineChapel HillUSA
  5. 5.Department of PathologyBrigham and Women’s HospitalBostonUSA
  6. 6.Department of Community and Family MedicineDartmouth-Hitchcock Medical CenterLebanonUSA
  7. 7.Department of PediatricsDartmouth-Hitchcock Medical CenterLebanonUSA

Personalised recommendations