Abstract
Malignancies are one of the leading causes of mortality in women during their reproductive life. Treatment of gynecological malignant tumors during pregnancy is possible but not simple, since it creates a conflict between care of the mother and the fetus. BC is the most prevalent malignancy diagnosed in pregnancy, ranking up to 21% of all pregnancy-related malignancies. Due to its stets increasing prevalence, aggressive cancer subtype, and severe ethical and psychological aspects linked to the disease, experts raise an alarm for an acute necessity to improve the overall management of the PABC—the issue which has strongly motivated our current paper. Comprehensive research data and clinical experience accumulated in recent years have advanced our understanding of the disease complexity. PABC treatment must be individualized with an emphasis on optimal care of the mother, while observing standard treatment protocols with regard to safety of the fetus. Treatment protocols should be elaborated based on the individualized patient profile, bearing in mind the acute danger to the mother, maximizing the therapy efficacy and minimizing harmful effects to the fetus. Complex consulting on treatment options, their impacts on pregnancy and potential teratogenic effects requires tight “doctor-patient” collaboration. Complications that may arise due to the treatment of breast cancer in pregnancy require a multiprofessional expertise including oncologists, neonatologists, perinatologists, obstetricians, teratologists, and toxicologists, and an extensive psychological support throughout the pregnancy and after giving birth. Thereby, specifically psychological aspects of PABC diagnosis and follow-up are frequently neglected, being not yet adequately explored in the entire disease management approach. Herewith, we update the status quo regarding the currently available diagnostic modalities, complex treatment algorithms, and novel clinical approaches which altogether argue for an urgent necessity of a paradigm shift moving away from reactive to predictive, preventive, and personalized medical approach in the overall management of PABC meeting the needs of young populations, persons at high risk, affected patients, and families as the society at large.
We’re sorry, something doesn't seem to be working properly.
Please try refreshing the page. If that doesn't work, please contact support so we can address the problem.
References
Golubnitschaja O, Debald M, Yeghiazaryan K, Kuhn W, Pešta M, Costigliola V, et al. Breast cancer epidemic in the early 21st century: evaluation of risk factors, cumulative questionnaires and recommendations for preventive measures. Tumor Biol. 2016;37(10):12941–57.
Triunfo S, Scambia G. Cancer in pregnancy: diagnosis, treatment and neonatal outcome. Minerva Ginecol. 2014;66(3):325–34.
Lee YY, Roberts CL, Dobbins T, Stavrou E, Black K, Morris J, et al. Incidence and outcomes of pregnancy-associated cancer in Australia, 1994-2008: a population-based linkage study. BJOG. 2012;119(13):1572–82.
Polivka J, Altun I, Golubnitschaja O. Pregnancy-associated breast cancer: the risky status quo and new concepts of predictive medicine. EPMA J. 2018;9(1):1–13.
Johansson AL, Andersson TM, Hsieh CC, Cnattingius S, Dickman PW, Lambe M. Family history and risk of pregnancy-associated breast cancer (PABC). Breast Cancer Res Treat. 2015;151(1):209–17.
Keyser EA, Staat BC, Fausett MB, Shields AD. Pregnancy-associated breast Cancer. Rev Obstet Gynec. 2012;5(2):94–9.
McGrath SE, Ring A. Chemotherapy for breast cancer in pregnancy: evidence and guidance for oncologists. Ther Adv Med Oncol. 2011;3(2):73–83.
Vinatier E, Merlot B, Poncelet E, Collinet P, Vinatier D. Breast Cancer during pregnancy. Eur J Obstet Gynecol Reprod Biol. 2009;147(1):9–14.
Gupta PB, Kuperwasser CJ. Contributions of estrogen to ER-negative breast tumor growth. Steroid Biochem Mol Biol. 2006;102(1–5):71–8.
John EM, Hines LM, Phipps AI, Koo J, Longacre TA, Ingles SA, et al. Reproductive history, breast-feeding and risk of triple negative breast cancer: the breast Cancer etiology in minorities (BEM) study. Int J Cancer. 2018;142(11):2273–85.
Azim HA Jr, Pavlidis N, Peccatori FA. Treatment of the pregnant mother with cancer: a systematic review on the use of cytotoxic, endocrine, targeted agents and immunotherapy during pregnancy. Part II: hematological tumors. Cancer Treat Rev. 2010;36(2):110–21.
Muñoz-Rodríguez JL, Vrba L, Futscher BW, Hu C, Komenaka IK, Meza-Montenegro MM, et al. Differentially expressed microRNAs in postpartum breast cancer in Hispanic women. PLoS One. 2015;10(4):e0124340.
Golubnitschaja O, Baban B, Boniolo G, Wang W, Bubnov R, Kapalla M, et al. Medicine in the early twenty-first century: paradigm and anticipation - EPMA position paper 2016. EPMA J. 2016;7:23.
Golubnitschaja O, Costigliola V, Grech G. EPMA World Congress: traditional forum in predictive, preventive and personalised medicine for multi-professional consideration and consolidation. EPMA J. 2017;8(Suppl):1–54.
Yu HH, Cheung PS, Leung RC, Leung TN, Kwan WH. Current management of pregnancy-associated breast cancer. Hong Kong Med J. 2017;23(4):387–94.
Ahn BY, Kim HH, Moon WK, Pisano ED, Kim HS, Cha ES, et al. Pregnancy- and-lactation-associated breast cancer: mammographic and sonographic findings. J Ultrasound Med. 2003;22(5):491–7.
Theriault RL, Litton JK. Pregnancy during or after breast cancer diagnosis: what do we know and what do we need to know? J Clin Oncol. 2013;31(20):2521.
Litton JK, Theriault RL, Gonzalez-Angulo AM. Breast cancer diagnosis during pregnancy. Women's Health (Lond Engl). 2009;5(3):243–9.
Kanal E, Barkovich AJ, Bell C, Borgstede JP, Bradley WG Jr, Froelich JW, et al. ACR blue ribbon panel on MR safety. ACR guidance document for safe MR practices: 2007. AJR Am J Roentgenol. 2007;188(6):1447–74.
Sundgren PC, Leander P. Is administration of gadolinium-based contrast media to pregnant women and small children justified? J Magn Reson Imaging. 2011;34(4):750–7.
Heymann JJ, Halligan AM, Hoda SA, Facey KE, Hoda RS. Fine needle aspiration of breast masses in pregnant and lactating women: experience with 28 cases emphasizing Thinprep findings. Diagn Cytopathol. 2015;43(3):188–94.
Mitra S, Dey P. Fine-needle aspiration and core biopsy in the diagnosis of breast lesions: a comparison and review of the literature. Cytojournal. 2016;13:18.
Nettleton J, Long J, Kuban D, Wu R, Shaefffer J, El-Mahdi A. Breast cancer during pregnancy: quantifying the risk of treatment delay. Obstet Gynecol. 1996;87(3):414–8.
Szecsi PB, Andersen MR, Bjørngaard B, Hedengran KK, Stender S. Cancer antigen 125 after delivery in women with normal pregnancy: a prospective cohort study. Acta Obstet Gynecol Scand. 2014;93(12):1295–301.
Han SN, Lotgerink A, Gziri MM, Van Calsteren K, Hanssens M, Amant F. Physiologic variations of serum tumor markers in gynecological malignancies during pregnancy: a systematic review. BMC Med. 2012;8(10):86.
Moore RG, Miller MC, Eklund EE, Lu KH, Bast RC Jr, Lambert-Messerlian G. Serum levels of the ovarian cancer biomarker HE4 are decreased in pregnancy and increase with age. Am J Obstet Gynecol. 2012;206(4):349.e1–7.
Weber JA, Baxter DH, Zhang S, Huang DY, Huang KH, Lee MJ, et al. The microRNA spectrum in 12 body fluids. Clin Chem. 2010;56(11):1733–41.
Jayasinghe Y. Preventive care and evaluation of the adolescent with a breast mass. Semin Plast Surg. 2013;27(1):13–8.
Bick U. Intensified surveillance for early detection of breast cancer in high-risk patients. Breast Care (Basel). 2015;10(1):13–20.
Amir E, Freedman OC, Seruga B, Evans DG. Assessing women at high risk of breast cancer: a review of risk assessment models. J Natl Cancer Inst. 2010;102(10):680–91.
Corsini C, Henouda S, Nejima DB, Bertet H, Toledano A, Boussen H, et al. Early onset breast cancer: differences in risk factors, tumor phenotype, and genotype between north African and south European women. Breast Cancer Res Treat. 2017;166(2):631–9.
Zubor P, Gondova A, Polivka J, Kasajova P, Konieczka K, Danko J, et al. Breast cancer and Flammer syndrome: any symptoms in common for prediction, prevention and personalised medical approach? EPMA J. 2017;8(2):129–40.
Bubnov R, Polivka J, Zubor P, Konieczka K, Golubnitschaja O. “Pre-metastatic niches” in breast cancer: are they created by or prior to the tumour onset? “Flammer syndrome” relevance to address the question. EPMA J. 2017;8(2):141–57.
Smokovski I, Risteski M, Polivka J, Zubor P, Konieczka K, Costigliola V, et al. Postmenopausal breast cancer: European challenge and innovative concepts. EPMA J. 2017;8(2):159–69.
Marmot MG, Altman DG, Cameron DA, Dewar JA, Thompson SG, Wilcox M. The benefits and harms of breast cancer screening: an independent review. Br J Cancer. 2013;108(11):2205–40.
Girotra S, Yeghiazaryan K, Golubnitschaja O. Potential biomarker panels in overall breast cancer management: advancements by multilevel diagnostics. Per Med. 2016;13:469–84.
Maltoni R, Fici P, Amadori D, Gallerani G, Cocchi C, Zoli M, et al. Circulating tumor cells in early breast cancer: a connection with vascular invasion. Cancer Lett. 2015;367(1):43–8.
Chan CWH, Law BMH, So WKW, Chow KM, Waye MMY. Novel strategies on personalized medicine for breast Cancer treatment: an update. Int J Mol Sci. 2017;18(11):E2423.
Grech G, Zhan X, Yoo BC, Bubnov R, Hagan S, Danesi R, et al. Desiderio DM. EPMA position paper in cancer: current overview and future perspectives. EPMA J. 2015;6(1):9.
Cardonick E, Iacobucci A. Use of chemotherapy during human pregnancy. Lancet Oncol. 2004;5(5):283–91.
Azim HA Jr, Azim H, Peccatori FA. Treatment of cancer during pregnancy with monoclonal antibodies: a real challenge. Expert Rev Clin Immunol. 2010;6(6):821–6.
Ji YI, Kim KT. Gynecologic malignancy in pregnancy. Obstet Gynecol Sci. 2013;56(5):289–300.
Moran BJ, Yano H, Al Zahir N, Farquharson M. Conflicting priorities in surgical intervention for cancer in pregnancy. Lancet Oncol. 2007;8(6):536–44.
Gentilini O, Cremonesi M, Toesca A, Colombo N, Peccatori F, Sironi R, et al. Sentinel lymph node biopsy in pregnant patients with breast cancer. Eur J Nucl Med Mol Imaging. 2010;37(1):78–83.
Kuerer HM, Gwyn K, Ames FC, Theriault RL. Conservative surgery and chemotherapy for breast carcinoma during pregnancy. Surgery. 2002;131(1):108–10.
Dominici LS, Kuerer HM, Babiera G, Hahn KM, Perkins G, Middleton L, et al. Wound complications from surgery in pregnancy- associated breast cancer (PABC). Breast Dis. 2010;31(1):1–5.
Khera SY, Kiluk JV, Hasson DM, Meade TL, Meyers MP, Dupont EL, et al. Pregnancy-associated breast cancer patients can safely undergo lymphatic mapping. Breast J. 2008;14(3):250–4.
Amant F, Halaska MJ, Fumagalli M, Dahl Steffensen K, Lok C, Van Calsteren K, et al. ESGO task force ‘Cancer in pregnancy’. Gynecologic cancers in pregnancy: guidelines of a second international consensus meeting. Int J Gynecol Cancer. 2014;24(3):394–403.
Greskovich JF Jr, Macklis RM. Radiation therapy in pregnancy: risk calculation and risk minimization. Semin Oncol. 2000;27(6):633–45.
Rovera F, Chiappa C, Coglitore A, Baratelli GM, Fachinetti A, Marelli M, et al. Management of breast cancer during pregnancy. Int J Surg. 2013;11(Suppl 1):S64–8.
Amant F, Deckers S, Van Calsteren K, Loibl S, Halaska M, Brepoels L, et al. Breast cancer in pregnancy: recommendations of an international consensus meeting. Eur J Cancer. 2010;46(18):3158–68.
Cardonick E. Pregnancy-associated breast cancer: optimal treatment options. Int J Womens Health. 2014;6:935–43.
Hershman DL, Wang X, McBride R, Jacobson JS, Grann VR, Neugut AI. Delay in initiating adjuvant radiotherapy following breast conservation surgery and its impact on survival. Int J Radiat Oncol Biol Phys. 2006;65(5):1353–60.
Chen Z, King W, Pearcey R, Kerba M, Mackillop WJ. The relationship between waiting time for radiotherapy and clinical outcomes: a systematic review of the literature. Radiother Oncol. 2008;87(1):3–16.
Espie M, Cuvier C. Treating breast cancer during pregnancy – what can be taken safely. Drug Saf. 1998;2(18):135–42.
Han SN, Van Calsteren K, Heyns L, Mhallem Gziri M, Amant F. Breast cancer during pregnancy: a literature review. Minerva Ginecol. 2010;62(6):585–97.
Levy S, Fayez I, Taguchi N, Han JY, Aiello J, Matsui D, et al. Pregnancy outcome following in utero exposure to bisphosphonates. Bone. 2009;44(3):428–30.
Padmagirison R, Gajjar K, Spencer C. Management of breast cancer during pregnancy. Obstet Gynaecol. 2010;12:186–92.
de Haan J, Verheecke M, Van Calsteren K, Van Calster B, Shmakov RG, Mhallem Gziri M, et al. Oncological management and obstetric and neonatal outcomes for women diagnosed with cancer during pregnancy: a 20-year international cohort study of 1170 patients. Lancet Oncol. 2018;19(3):337–46.
Azim HA Jr, Del Mastro L, Scargone G, Peccatori FA. Treatment of breast cancer during pregnancy: regimen selection, pregnancy monitoring and more…. Breast. 2011;20(1):1–6.
Krishna I, Lindsay M. Breast cancer in pregnancy. Obstet Gynecol Clin North Am. 2013;40(3):559–71.
Framarino-Dei-Malatesta M, Sammartino P, Napoli A. Does anthracycline-based chemotherapy in pregnant women with cancer offer safe cardiac and neurodevelopmental outcomes for the developing fetus? BMC Cancer. 2017;17(1):777.
Mir O, Berveiller P. Increased evidence for use of chemotherapy in pregnancy. Lancet Oncol. 2012;13(9):852–4.
Zagouri F, Sergentanis TN, Chrysikos D, Dimitrakakis C, Tsigginou A, Zografos CG, et al. Taxanes for breast cancer during pregnancy: a systematic review. Clin Breast Cancer. 2013;13(1):16–23.
Zagouri F, Dimitrakakis C, Marinopoulos S, Tsigginou A, Dimopoulos MA. Cancer in pregnancy: disentangling treatment modalities. ESMO Open. 2016;1(3):e000016.
Negro A, Brar BK, Gu Y, Peterson KL, Vale W, Lee KF. ErbB2 is required for G protein-coupled receptor signaling in the heart. Proc Natl Acad Sci U S A. 2006;103(43):15889–93.
Goodyer MJ, Ismail JR, O’Reilly SP, Moylan EJ, Ryan CA, Hughes PA, et al. Safety of trastuzumab (Herceptin) during pregnancy: two case reports. Cases J. 2009;2:9329.
Pant S, Landon MB, Blumenfeld M, Farrar W, Shapiro CL. Treatment of breast cancer with trastuzumab during pregnancy. J Clin Oncol. 2008;26(9):1567–9.
Pirvulescu C, Mau C, Schultz H, Sperfeld A, Isbruch A, Renner-Lützkendorf H, et al. Breast Cancer during pregnancy: an interdisciplinary approach in our institution. Breast Care (Basel). 2012;7(4):311–4.
El-Safadi S, Wuesten O, Muenstedt K. Primary diagnosis of metastatic breast cancer in the third trimester of pregnancy: a case report and review of the literature. J Obstet Gynaecol Res. 2012;38(3):589–92.
Mandrawa CL, Stewart J, Fabinyi GC, Walker SP. A case study of trastuzumab treatment for metastatic breast cancer in pregnancy: fetal risks and management of cerebral metastases. Aust N Z J Obstet Gynaecol. 2011;51(4):372–6.
Amant F, von Minckwitz G, Han SN, Bontenbal M, Ring AE, Giermek J, et al. Prognosis of women with primary breast cancer diagnosed during pregnancy: results from an international collaborative study. J Clin Oncol. 2013;31(20):2532–9.
Pauli SA, Tang H, Wang J, Bohlen P, Posser R, Hartman T, et al. The vascular endothelial growth factor (VEGF)/VEGF receptor 2 pathway is critical for blood vessel survival in corpora lutea of pregnancy in the rodent. Endocrinology. 2005;146(3):1301–11.
Demir R, Kayisli UA, Seval Y, Celik-Ozenci C, Korgun ET, Demir-Weusten AY, et al. Sequential expression of VEGF and its receptors in human placental villi during very early pregnancy: differences between placental vasculogenesis and angiogenesis. Placenta. 2004;25(6):560–72.
Chen HX, Cleck JN. Adverse effects of anticancer agents that target the VEGF pathway. Nat Rev. 2009;6(8):465–77.
Berkane N. Gestational hypertensions: definitions and consequences in outcome of pregnancy. Ann Fr Anesth Reanim. 2010;29(3):e1–6.
Ishizuka S, Satou S. A case of delivery of healthy infant in breast cancer patient incidentally treated with goserelin acetate and tamoxifen during pregnancy. Breast Cancer. 2016;23(1):164–6.
RCOG Green-top guideline No. 12. Pregnancy and breast cancer. UK royal college of obstetricians and Gynaecologists; 2011.
Bahrami A, Aledavood A, Anvari K, Hassanian SM, Maftouh M, Yaghobzade A, et al. The prognostic and therapeutic application of microRNAs in breast cancer: tissue and circulating microRNAs. J Cell Physiol. 2018;233(2):774–86.
Esquela-Kerscher A, Slack FJ. Oncomirs - microRNAs with a role in cancer. Nat Rev Cancer. 2006;6(4):259–69.
Walter BA, Gómez-Macias G, Valera VA, Sobel M, Merino MJ. miR-21 expression in pregnancy-associated breast Cancer: a possible marker of poor prognosis. J Cancer. 2011;2:67–75.
Eedarapalli P, Jain S. Breast cancer in pregnancy. J Obstet Gynaecol. 2009;26(1):1–4.
Ha JF, Longnecker N. Doctor-patient communication: a review. Ochsner J. 2010;10(1):38–43.
Perry S, Kowalski TL, Chang CH. Quality of life assessment in women with breast cancer, benefits, acceptability and utilization. Health Qual Life Outcomes. 2007;5:24.
Avis NE, Crawford S, Manuel J. Quality of life among younger women with breast cancer. J Clin Oncol. 2005;23(15):3322–30.
Rodsten JM Understanding the experience of pregnancy-associated breast Cancer - an interpretative phenomenological analysis. In: DCounsPsych, University of the West of England. 2017. http://eprints.uwe.ac.uk/30561. Accessed 26 Jul 2017.
Hayes SC, Hofmann SG. The third wave of CBT and the rise of process-based care. World Psychiatry. 2017;16(3):245–6.
David D, Cristea I, Hofmann SG. Why cognitive behavioral therapy is the current gold standard of psychotherapy. Front Psychiatry. 2018;9:4.
Hofmann SG, Asnaani A, Vonk IJJ, Sawyer AT, Fang A. The efficacy of cognitive behavioral therapy: a review of meta-analyses. Cogn Ther Res. 2012;36(5):427–40.
Hofmann SG, Asmundson GJ, Beck AT. The science of cognitive therapy. Behav Ther. 2013;44(2):199–212.
Acknowledgements
This work has been supported by the following organizations: European Association for Predictive, Preventive, and Personalized Medicine, EPMA, Brussels, Belgium; Slovak Research and Development Agency (under contract no. APVV-16-0021), the Scientific Grant Agency, Ministry of Education, Science, and Research, Slovak Republic; and the VEGA Grant Agency (1/0124/17), Ministry of Education, Science and Research, Slovak Republic
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Not applicable.
Conflict of interest
The authors declare that they have no conflict of interest.
Statement of informed consent
Patients have not been involved in the study.
Statement of human and animal rights
No experiments have been performed including patients and/or animals.
Additional information
Pavol Zubor and Peter Kubatka co-first/equal authorship
Rights and permissions
About this article
Cite this article
Zubor, P., Kubatka, P., Kapustova, I. et al. Current approaches in the clinical management of pregnancy-associated breast cancer—pros and cons. EPMA Journal 9, 257–270 (2018). https://doi.org/10.1007/s13167-018-0139-5
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s13167-018-0139-5