Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress 2023 EHA Congress 2023 ASCO Annual Meeting
Clinical Collections
Advances in Alzheimer’s

At a glance: The ONWARDS insulin icodec trials

A round-up of the ONWARDS phase 3 clinical trials evaluating the novel weekly insulin icodec in people with diabetes.
ADVANCED SEARCH
Log in
Top
Breast Cancer Research
Published in: Breast Cancer Research 1/2016

Open Access 01-12-2016 | Review

Breast cancer and social environment: getting by with a little help from our friends

Authors: Adam Hinzey, Monica M. Gaudier-Diaz, Maryam B. Lustberg, A. Courtney DeVries

Published in: Breast Cancer Research | Issue 1/2016

Login to get access

Abstract

Social environment is a well-recognized determinant in health and wellbeing. Among breast cancer patients, inadequate social support is associated with a substantial increase in cancer-related mortality. A common explanation is that socially isolated individuals fare worse due to reduced instrumental support (i.e., assistance meeting the demands of treatment). However, the ability to replicate the detrimental effects of social isolation on mammary tumor growth in rodents strongly suggests an alternative explanation; i.e., socially isolated individuals have a physiological milieu that promotes tumor growth. This review summarizes the clinical and basic science literature supporting social influences on breast cancer, and provides a conceptual physiological framework for these effects. We propose that social environment contributes to the vast individual differences in prognosis among breast cancer survivors because social environment is capable of altering basic physiological processes, which in turn can modulate tumor growth. Appreciation of the role of social environment in breast cancer progression could promote the identification of patients at increased risk for poor outcomes. In addition, characterization of the underlying physiological mechanisms could lead to targeted disruption of detrimental pathways that promote tumor progression in socially isolated individuals, or exploitation of protective pathways activated through social engagement as novel therapeutic complements to contemporary treatments.
Literature
1.
2.
3.
Kroenke CH, Kubzansky LD, Schernhammer ES, Holmes MD, Kawachi I. Social networks, social support, and survival after breast cancer diagnosis. J Clin Oncol. 2006;24:1105–11.CrossRefPubMed
4.
Lutgendorf SK, De Geest K, Bender D, Ahmed A, Goodheart MJ, Dahmoush L, Zimmerman MB, Penedo FJ, Lucci JA, Ganjei-Azar P, Thaker PH, Mendez L, Lubaroff DM, Slavich GM, Cole SW, Sood AK. Social influences on clinical outcomes of patients with ovarian cancer. J Clin Oncol. 2012;30:2885–90.
5.
Berkman LF, Syme SL. Social networks, host resistance, and mortality: a nine-year follow-up study of Alameda County residents. Am J Epidemiol. 1979;109:186–204.PubMed
6.
Berkman LF, Glass T, Brissette I, Seeman TE. From social integration to health: Durkheim in the new millennium. Soc Sci Med. 2000;51:843–57.CrossRefPubMed
7.
Tomaka J, Thompson S, Palacios R. The relation of social isolation, loneliness, and social support to disease outcomes among the elderly. J Aging Health. 2006;18:359–84.CrossRefPubMed
8.
Steptoe A, Shankar A, Demakakos P, Wardle J. Social isolation, loneliness, and all-cause mortality in older men and women. Proc Natl Acad Sci U S A. 2013;110:5797–801.CrossRefPubMedPubMedCentral
9.
Umberson D. Family status and health behaviors: social control as a dimension of social integration. J Health Soc Behav. 1987;28:306–19.CrossRefPubMed
10.
Cohen S, Wills TA. Stress, social support, and the buffering hypothesis. Psychol Bull. 1985;98:310–57.CrossRefPubMed
11.
Karelina K, DeVries AC. Modeling social influences on human health. Psychosom Med. 2011;73:67–74.CrossRefPubMed
12.
Jemmott JB, Locke SE. Psychosocial factors, immunologic mediation, and human susceptibility to infectious diseases: how much do we know? Psychol Bull. 1984;95:78–108.CrossRefPubMed
13.
Nausheen B, Gidron Y, Peveler R, Moss-Morris R. Social support and cancer progression: a systematic review. J Psychosom Res. 2009;67:403–15.CrossRefPubMed
14.
Falagas ME, Zarkadoulia EA, Ioannidou EN, Peppas G, Christodoulou C, Rafailidis PI. The effect of psychosocial factors on breast cancer outcome: a systematic review. Breast Cancer Res. 2007;9:R44.CrossRefPubMedPubMedCentral
15.
Kroenke CH, Quesenberry C, Kwan ML, Sweeney C, Castillo A, Caan BJ. Social networks, social support, and burden in relationships, and mortality after breast cancer diagnosis in the Life After Breast Cancer Epidemiology (LACE) study. Breast Cancer Res Treat. 2013;137:261–71.CrossRefPubMed
16.
Beasley JM, Newcomb PA, Trentham-Dietz A, Hampton JM, Ceballos RM, Titus-Ernstoff L, Egan KM, Holmes MD. Social networks and survival after breast cancer diagnosis. J Cancer Surviv. 2010;4:372–80.
17.
Weihs KL, Enright TM, Simmens SJ. Close relationships and emotional processing predict decreased mortality in women with breast cancer: preliminary evidence. Psychosom Med. 2008;70:117–24.CrossRefPubMed
18.
Kroenke CH, Michael Y, Tindle H, Gage E, Chlebowski R, Garcia L, Messina C, Manson JE, Caan BJ. Social networks, social support and burden in relationships, and mortality after breast cancer diagnosis. Breast Cancer Res Treat. 2012;133:375–85.
19.
Leung J, Pachana NA, McLaughlin D. Social support and health-related quality of life in women with breast cancer: a longitudinal study. Psychooncology. 2014;23:1014–20.CrossRefPubMed
20.
Ell K, Nishimoto R, Mediansky L, Mantell J, Hamovitch M. Social relations, social support and survival among patients with cancer. J Psychosom Res. 1992;36:531–41.CrossRefPubMed
21.
Weihs KL, Simmens SJ, Mizrahi J, Enright TM, Hunt ME, Siegel RS. Dependable social relationships predict overall survival in stages II and III breast carcinoma patients. J Psychosom Res. 2005;59(5):299–306.CrossRefPubMed
22.
Funch DP, Marshall J. The role of stress, social support and age in survival from breast cancer. J Psychosom Res. 1983;27:77–83.CrossRefPubMed
23.
Lutgendorf SK, Andersen BL. Biobehavioral approaches to cancer progression and survival: mechanisms and interventions. Am Psychol. 2015;70(2):186–97.CrossRefPubMedPubMedCentral
24.
Williams JB, Pang D, Delgado B, Kocherginsky M, Tretiakova M, Krausz T, Pan D, He J, McClintock MK, Conzen SD. A model of gene-environment interaction reveals altered mammary gland gene expression and increased tumor growth following social isolation. Cancer Prev Res (Phila). 2009;2:850–61.
25.
Hermes GL, Delgado B, Tretiakova M, Cavigelli SA, Krausz T, Conzen SD, McClintock MK. Social isolation dysregulates endocrine and behavioral stress while increasing malignant burden of spontaneous mammary tumors. Proc Natl Acad Sci U S A. 2009;106:22393–8.
26.
Adam EK, Hawkley LC, Kudielka BM, Cacioppo JT. Day-to-day dynamics of experience–cortisol associations in a population-based sample of older adults. Proc Natl Acad Sci U S A. 2006;103(45):17058–63.CrossRefPubMedPubMedCentral
27.
Giese-Davis J, Wilhelm FH, Tamagawa R, Palesh O, Neri E, Taylor CB, Kraemer HC, Spiegel D. Higher vagal activity as related to survival in patients with advanced breast cancer: an analysis of autonomic dysregulation. Psychosom Med. 2015;77:346–55.
28.
Sephton SE, Sapolsky RM, Kraemer HC, Spiegel D. Diurnal cortisol rhythm as a predictor of breast cancer survival. J Natl Cancer Inst. 2000;92:994–1000.CrossRefPubMed
29.
Barron TI, Connolly RM, Sharp L, Bennett K, Visvanathan K. Beta blockers and breast cancer mortality: a population- based study. J Clin Oncol. 2011;29:2635–44.CrossRefPubMed
30.
Melhem-Bertrandt A, Chavez-Macgregor M, Lei X, Brown EN, Lee RT, Meric-Bernstam F, Sood AK, Conzen SD, Hortobagyi GN, Gonzalez-Angulo AM. Beta-blocker use is associated with improved relapse-free survival in patients with triple-negative breast cancer. J Clin Oncol. 2011;29:2645–52.
31.
Powe DG, Voss MJ, Zänker KS, Habashy HO, Green AR, Ellis IO, Entschladen F. Beta-blocker drug therapy reduces secondary cancer formation in breast cancer and improves cancer specific survival. Oncotarget. 2010;1:628–38.
32.
Sood AK, Bhatty R, Kamat AA, Landen CN, Han L, Thaker PH, Li Y, Gershenson DM, Lutgendorf S, Cole SW. Stress hormone-mediated invasion of ovarian cancer cells. Clin Cancer Res. 2006;12:369–75.
33.
Thaker PH, Han LY, Kamat AA, Arevalo JM, Takahashi R, Lu C, Jennings NB, Armaiz-Pena G, Bankson JA, Ravoori M, Merritt WM, Lin YG, Mangala LS, Kim TJ, Coleman RL, Landen CN, Li Y, Felix E, Sanguino AM, Newman RA, Lloyd M, Gershen-son DM, Kundra V, Lopez-Berestein G, Lutgendorf SK, Cole SW, Sood AK. Chronic stress promotes tumor growth and angiogenesis in a mouse model of ovarian carcinoma. Nat Med. 2006;12:939–44.
34.
Cole SW, Sood AK. Molecular pathways: beta-adrenergic signaling in cancer. Clin Cancer Res. 2012;18:1201–6.CrossRefPubMed
35.
Sloan EK, Priceman SJ, Cox BF, Yu S, Pimentel MA, Tangkanangnukul V, Arevalo JM, Morizono K, Karanikolas BD, Wu L, Sood AK, Cole SW. The sympathetic nervous system induces a metastatic switch in primary breast cancer. Cancer Res. 2010;70:7042–52.
36.
Lang K, Drell TL, Lindecke A, Niggemann B, Kaltschmidt C, Zaenker KS, Entschladen F. Induction of a metastatogenic tumor cell type by neurotransmitters and its pharmacological inhibition by established drugs. Int J Cancer. 2004;112:231–8.
37.
Masur K, Niggemann B, Zanker KS, Entschladen F. Norepinephrine-induced migration of SW 480 colon carcinoma cells is inhibited by beta-blockers. Cancer Res. 2001;61:2866–9.PubMed
38.
Lutgendorf SK, DeGeest K, Dahmoush L, Farley D, Penedo F, Bender D, Goodheart M, Buekers TE, Mendez L, Krueger G, Clevenger L, Lubaroff DM, Sood AK, Cole SW. Social isolation is associated with elevated tumor norepinephrine in ovarian carcinoma patients. Brain Behav Immun. 2011;25:250–5.
39.
Levy SM, Herberman RB, Lippman M, D’Angelo T, Lee J. Immunological and psychosocial predictors of disease recurrence in patients with early-stage breast cancer. Behav Med. 1991;17(2):67–75.CrossRefPubMed
40.
Levy SM, Herberman RB, Whiteside T, Sanzo K, Lee J, Kirkwood J. Perceived social support and tumor estrogen/progesterone receptor status as predictors of natural killer cell activity in breast cancer patients. Psychosom Med. 1990;52(1):73–85.CrossRefPubMed
41.
Gündisch S, Boeckeler E, Behrends U, Amtmann E, Ehrhardt H, Jeremias I. Glucocorticoids augment survival and proliferation of tumor cells. Anticancer Res. 2012;32:4251–61.PubMed
42.
Wu W, Pew T, Zou M, Pang D, Conzen SD. Glucocorticoid receptor-induced MAPK phosphatase-1 (MPK-1) expression inhibits paclitaxel-associated MAPK activation and contributes to breast cancer cell survival. J Biol Chem. 2005;280:4117–24.CrossRefPubMed
43.
Feng Z, Liu L, Zhang C, Zheng T, Wang J, Lin M, Zhao Y, Wang X, Levine AJ, Hu W. Chronic restraint stress attenuates p53 function and promotes tumorigenesis. Proc Natl Acad Sci U S A. 2012;109:7013–8.
44.
Pang D, Kocherginsky M, Krausz T, Kim SY, Conzen SD. Dexamethasone decreases xenograft response to Paclitaxel through inhibition of tumor cell apoptosis. Cancer Biol Ther. 2006;5:933–40.CrossRefPubMed
45.
Reeder A, Attar M, Nazario L, Bathula C, Zhang A, Hochbaum D, Roy E, Cooper KL, Oesterreich S, Davidson NE, Neumann CA, Flint MS. Stress hormones reduce the efficacy of paclitaxel in triple negative breast cancer through induction of DNA damage. Br J Cancer. 2015;112(9):1461–70.
46.
Skor MN, Wonder EL, Kocherginsky M, Goyal A, Hall BA, Cai Y, Conzen SD. Glucocorticoid receptor antagonism as a novel therapy for triple-negative breast cancer. Clin Cancer Res. 2013;19:6163–72.
47.
de Visser KE, Eichten A, Coussens LM. Paradoxical roles of the immune system during cancer development. Nat Rev Cancer. 2006;6:24–37.CrossRefPubMed
48.
49.
50.
Sørensen GV, Cronin-Fenton DP, Sørensen HT, Ulrichsen SP, Pedersen L, Lash TL. Use of glucocorticoids and risk of breast cancer: a Danish population-based case-control study. Breast Cancer Res. 2012;14:R21.CrossRefPubMedPubMedCentral
51.
Lietzen LW, Ahern T, Christiansen P, Jensen AB, Sørensen HT, Lash TL, Cronin-Fenton DP. Glucocorticoid prescriptions and breast cancer recurrence: a Danish nationwide prospective cohort study. Ann Oncol. 2014;25:2419–25.
52.
Wood WC, Budman DR, Korzun AH, Cooper MR, Younger J, Hart RD, Moore A, Ellerton JA, Norton L, Ferree CR, et al. Dose and dose intensity of adjuvant chemotherapy for stage II, node-positive breast carcinoma. N Engl J Med. 1994;330:1253–9.
53.
Grant N, Hamer M, Steptoe A. Social isolation and stress-related cardiovascular, lipid, and cortisol responses. Ann Behav Med. 2009;37:29–37.CrossRefPubMed
54.
Garssen B, Goodkin K. On the role of immunological factors as mediators between psychosocial factors and cancer progression. Psychiatry Res. 1999;85:51–61.CrossRefPubMed
55.
Madden KS, Szpunar MJ, Brown EB. Early impact of social isolation and breast tumor progression in mice. Brain Behav Immun. 2013;30(Suppl):S135–41.CrossRefPubMed
56.
Filiano AJ, Gadani SP, Huberts A, March J, Kipnis J. New insights into the role of T cells in autism spectrum disorder. Society for Neuroscience Annual Meeting 2014; Nanosymposium abstract 18.11.
57.
Volden PA, Wonder EL, Skor MN, Carmean CM, Patel FN, Ye H, Kocherginsky M, McClintock MK, Brady MJ, Conzen SD. Chronic social isolation is associated with metabolic gene expression changes specific to mammary adipose tissue. Cancer Prev Res (Phila). 2013;6:634–45.
58.
59.
Nilsson MB, Armaiz-Pena G, Takahashi R, Lin YG, Trevino J, Li Y, Jennings N, Arevalo J, Lutgendorf SK, Gallick GE, Sanguino AM, Lopez-Berestein G, Cole SW, Sood AK. Stress hormones regulate interleukin-6 expression by human ovarian carcinoma cells through a Src-dependent mechanism. J Biol Chem. 2007;282:29919–26.
60.
Shahzad MM, Arevalo JM, Armaiz-Pena GN, Lu C, Stone RL, Moreno-Smith M, Nishimura M, Lee JW, Jennings NB, Bottsford-Miller J, Vivas-Mejia P,Lutgendorf SK, Lopez-Berestein G, Bar-Eli M, Cole SW, Sood AK. Stress effects on FosB- and interleukin-8 (IL8)-driven ovarian cancer growth and metastasis. J Biol Chem. 2010;12(46):35462–70.
61.
Lutgendorf SK, Sood AK, Anderson B, McGinn S, Maiseri H, Dao M, Sorosky JI, De Geest K, Ritchie J, Lubaroff DM. Social support, psychological distress, and natural killer cell activity in ovarian cancer. J Clin Oncol. 2005;23(28):7105–13.
62.
Smith AS, Wang Z. Hypothalamic oxytocin mediates social buffering of the stress response. Biol Psychiatry. 2014;76:281–8.CrossRefPubMed
63.
Cassoni P, Sapino A, Negro F, Bussolati G. Oxytocin inhibits proliferation of human breast cancer cell lines. Virchows Arch. 1994;425:467–72.CrossRefPubMed
64.
Cassoni P, Marrocco T, Bussolati B, Allia E, Munaron L, Sapino A, Bussolati G. Oxytocin induces proliferation and migration in immortalized human dermal microvascular endothelial cells and human breast tumor-derived endothelial cells. Mol Cancer Res. 2006;4:351–9.
65.
Cassoni P, Marrocco T, Sapino A, Allia E, Bussolati G. Oxytocin synthesis within the normal and neoplastic breast: first evidence of a local peptide source. Int J Oncol. 2006;28:1263–8.PubMed
66.
Copland JA, Jeng YJ, Strakova Z, Ives KL, Hellmich MR, Soloff MS. Demonstration of functional oxytocin receptors in human breast Hs578T cells and their up-regulation through a protein kinase C-dependent pathway. Endocrinology. 1999;140:2258–67.PubMed
67.
Bussolati G, Cassoni P, Ghisolfi G, Negro F, Sapino A. Immunolocalization and gene expression of oxytocin receptors in carcinomas and non-neoplastic tissues of the breast. Am J Pathol. 1996;148:1895–903.PubMedPubMedCentral
68.
Thibonnier M, Conarty DM, Preston JA, Plesnicher CL, Dweik RA, Erzurum SC. Human vascular endothelial cells express oxytocin receptors. Endocrinology. 1999;140:1301–9.PubMed
69.
Szeto A, Nation DA, Mendez AJ, Dominguez-Bendala J, Brooks LG, Schneiderman N, McCabe PM. Oxytocin attenuates NADPH-dependent superoxide activity and IL-6 secretion in macrophages and vascular cells. Am J Physiol Endocrinol Metab. 2008;295:E1495–501.
70.
Oliveira-Pelegrin GR, Saia RS, Cárnio EC, Rocha MJ. Oxytocin affects nitric oxide and cytokine production by sepsis-sensitized macrophages. Neuroimmunomodulation. 2013;20:65–71.CrossRefPubMed
71.
Lamagna C, Aurrand-Lions M, Imhof BA. Dual role of macrophages in tumor growth and angiogenesis. J Leukoc Biol. 2006;80:705–13.CrossRefPubMed
72.
Leek RD, Harris AL. Tumor-associated macrophages in breast cancer. J Mammary Gland Biol Neoplasia. 2002;7:177–89.CrossRefPubMed
73.
McCullough ME, Churchland PS, Mendez AJ. Problems with measuring peripheral oxytocin: can the data on oxytocin and human behavior be trusted? Neurosci Biobehav Rev. 2013;37(8):1485–92.CrossRefPubMed
74.
Chan DS, Vieira AR, Aune D, Bandera EV, Greenwood DC, McTiernan A, Navarro Rosen-blatt D, Thune I, Viera R, Norat T. Body mass index and survival in women with breast cancer-systematic literature review and meta-analysis of 82 follow-up studies. Ann Oncol. 2014;10:1901–14.
75.
Izano M, Satariano WA, Hiatt RA, Braithwaite D. Smoking and mortality after breast cancer diagnosis: the health and functioning women study. Cancer Med. 2015;2:315–24.CrossRef
Metadata
Title
Breast cancer and social environment: getting by with a little help from our friends
Authors
Adam Hinzey
Monica M. Gaudier-Diaz
Maryam B. Lustberg
A. Courtney DeVries
Publication date
01-12-2016
Publisher
BioMed Central
Published in
Breast Cancer Research / Issue 1/2016
Electronic ISSN: 1465-542X
DOI
https://doi.org/10.1186/s13058-016-0700-x

Other articles of this Issue 1/2016

Breast Cancer Research 1/2016 Go to the issue

Research article

Heterogeneity in global gene expression profiles between biopsy specimens taken peri-surgically from primary ER-positive breast carcinomas

Research article

Psychological stress, adverse life events and breast cancer incidence: a cohort investigation in 106,000 women in the United Kingdom

Research article

Outcomes of contralateral prophylactic mastectomy in relation to familial history: a decision analysis (BRCR-D-16-00033)

Research article

SHP2 acts both upstream and downstream of multiple receptor tyrosine kinases to promote basal-like and triple-negative breast cancer

Research Article

Does primary neoadjuvant systemic therapy eradicate minimal residual disease? Analysis of disseminated and circulating tumor cells before and after therapy

Research article

Combination of Paclitaxel and MG1 oncolytic virus as a successful strategy for breast cancer treatment
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Watch now

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine
Image Credits