Abstract
Purpose
TGF-β plays a dual role in breast carcinogenesis, acting at early stages as tumor-suppressors and later as tumor-promoters. TGF-β isoforms are expressed in breast tissues and secreted in milk, suggesting that analysis of levels in milk might be informative for breast cancer risk. Accordingly, we assessed TGF-β2 levels in milk from women who had undergone a breast biopsy and related the concentrations to diagnosis.
Methods
Milk donated by women who had undergone or were scheduled for a breast biopsy was shipped on ice for processing and testing. Breast cancer risk factors were obtained through a self-administered questionnaire, and biopsy diagnoses were extracted from pathology reports. TGF-β2 levels in milk, assessed as absolute levels and in relation to total protein, were analyzed in bilateral samples donated by 182 women. Linear regression was used to estimate relationships of log-transformed TGF-β2 levels and TGF-β2/ total protein ratios to biopsy category.
Results
Milk TGF-β2 levels from biopsied and non-biopsied breasts within women were highly correlated (r 2 = 0.77). Higher mean TGF-β2 milk levels (based on average of bilateral samples) were marginally associated with more severe breast pathological diagnosis, after adjusting for duration of nursing current child (adjusted p trend = 0.07).
Conclusions
Our exploratory analysis suggests a borderline significant association between higher mean TGF-β2 levels in breast milk and more severe pathologic diagnoses. Further analysis of TGF-β signaling in milk may increase understanding of postpartum remodeling and advance efforts to analyze milk as a means of assessing risk of breast pathology.
Similar content being viewed by others
References
Brinton LA, Sherman ME, Carreon JD, Anderson WF (2008) Recent trends in breast cancer among younger women in the United States. J Natl Cancer Inst 100:1643–1648
Anderson WF, Jatoi I, Sherman ME (2009) Qualitative age interactions in breast cancer studies: mind the gap. J Clin Oncol 27:5308–5311
Colleoni M, Anders CK (2013) Debate: the biology of breast cancer in young women is unique. Oncologist 18:e13–e15
Faupel-Badger JM, Arcaro KF, Balkam JJ, Eliassen AH, Hassiotou F et al (2013) Postpartum remodeling, lactation, and breast cancer risk: summary of a National Cancer Institute-sponsored workshop. J Natl Cancer Inst 105:166–174
Flanders KC, Wakefield LM (2009) Transforming growth factor-(beta)s and mammary gland involution; functional roles and implications for cancer progression. J Mammary Gland Biol Neoplasia 14:131–144
Monks J (2007) TGFbeta as a potential mediator of progesterone action in the mammary gland of pregnancy. J Mammary Gland Biol Neoplasia 12:249–257
Pardali K, Moustakas A (2007) Actions of TGF-beta as tumor suppressor and pro-metastatic factor in human cancer. Biochim Biophys Acta 1775:21–62
Massague J (2008) TGFbeta in Cancer. Cell 134:215–230
Drabsch Y, ten Dijke P (2011) TGF-beta signaling in breast cancer cell invasion and bone metastasis. J Mammary Gland Biol Neoplasia 16:97–108
Roberts AB, Wakefield LM (2003) The two faces of transforming growth factor beta in carcinogenesis. Proc Natl Acad Sci USA 100:8621–8623
Principe DR, Doll JA, Bauer J, Jung B, Munshi HG et al (2014) TGF-beta: duality of function between tumor prevention and carcinogenesis. J Natl Cancer Inst 106:djt369
Figueroa JD, Flanders KC, Garcia-Closas M, Anderson WF, Yang XR et al (2010) Expression of TGF-beta signaling factors in invasive breast cancers: relationships with age at diagnosis and tumor characteristics. Breast Cancer Res Treat 121:727–735
Hinshelwood RA, Huschtscha LI, Melki J, Stirzaker C, Abdipranoto A et al (2007) Concordant epigenetic silencing of transforming growth factor-beta signaling pathway genes occurs early in breast carcinogenesis. Cancer Res 67:11517–11527
Arcaro KF, Anderton DL (2008) Potential of using breast milk as a tool to study breast cancer and breast cancer risk. Future Oncol 4:595–597
Oddy WH, Rosales F (2010) A systematic review of the importance of milk TGF-beta on immunological outcomes in the infant and young child. Pediatr Allergy Immunol 21:47–59
Penttila IA (2010) Milk-derived transforming growth factor-beta and the infant immune response. J Pediatr 156:S21–S25
Namachivayam K, Blanco CL, Frost BL, Reeves AA, Jagadeeswaran R et al (2013) Preterm human milk contains a large pool of latent TGF-beta, which can be activated by exogenous neuraminidase. Am J Physiol Gastrointest Liver Physiol 304:G1055–G1065
Hawkes JS, Bryan DL, Gibson RA (2002) Variations in transforming growth factor beta in human milk are not related to levels in plasma. Cytokine 17:182–186
Kondo N, Suda Y, Nakao A, Oh-Oka K, Suzuki K et al (2011) Maternal psychosocial factors determining the concentrations of transforming growth factor-beta in breast milk. Pediatr Allergy Immunol 22:853–861
Tomicic S, Johansson G, Voor T, Bjorksten B, Bottcher MF et al (2010) Breast milk cytokine and IgA composition differ in Estonian and Swedish mothers—relationship to microbial pressure and infant allergy. Pediatr Res 68:330–334
Collado MC, Laitinen K, Salminen S, Isolauri E (2012) Maternal weight and excessive weight gain during pregnancy modify the immunomodulatory potential of breast milk. Pediatr Res 72:77–85
Qin W, Zhang K, Kliethermes B, Ruhlen RL, Browne EP et al (2012) Differential expression of cancer associated proteins in breast milk based on age at first full term pregnancy. BMC Cancer 12:100
Qin W, Zhang K, Kliethermes B, Amjad R, Clarke K et al (2013) Differential expression of cancer-associated proteins in breastmilk. Breastfeed Med 8:120–126
Arcaro KF, Browne EP, Qin W, Zhang K, Anderton DL et al (2012) Differential expression of cancer-related proteins in paired breast milk samples from women with breast cancer. J Hum Lact 28:543–546
Browne EP, Punska EC, Lenington S, Otis CN, Anderton DL et al (2011) Increased promoter methylation in exfoliated breast epithelial cells in women with a previous breast biopsy. Epigenetics 6:1425–1435
Dave H, Trivedi S, Shah M, Shukla S (2011) Transforming growth factor beta 2: a predictive marker for breast cancer. Indian J Exp Biol 49:879–887
Soufla G, Porichis F, Sourvinos G, Vassilaros S, Spandidos DA (2006) Transcriptional deregulation of VEGF, FGF2, TGF-beta1, 2, 3 and cognate receptors in breast tumorigenesis. Cancer Lett 235:100–113
Moses H, Barcellos-Hoff MH (2011) TGF-beta biology in mammary development and breast cancer. Cold Spring Harb Perspect Biol 3:a003277
Laverty HG, Wakefield LM, Occleston NL, O’Kane S, Ferguson MW (2009) TGF-beta3 and cancer: a review. Cytokine Growth Factor Rev 20:305–317
Baumgartel KL, Conley YP (2013) The utility of breastmilk for genetic or genomic studies: a systematic review. Breastfeed Med 8:249–256
Acknowledgments
This work was supported by awards from the CDMRP (W81XWH-08-1-0721) and The Avon Foundation for Women to KFA and the Intramural Research Program of NCI’s Division of Cancer Epidemiology and Genetics.
Conflict of interest
The authors declare that they have no conflict of interests.
Author information
Authors and Affiliations
Corresponding author
Additional information
The content of this publication does not necessarily reflect the views or policies of the US Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the US Government.
Electronic supplementary material
Below is the link to the electronic supplementary material.
Rights and permissions
About this article
Cite this article
Yang, H.P., Schneider, S.S., Chisholm, C.M. et al. Association of TGF-β2 levels in breast milk with severity of breast biopsy diagnosis. Cancer Causes Control 26, 345–354 (2015). https://doi.org/10.1007/s10552-014-0498-8
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10552-014-0498-8