Abstract
The objective of this study is to evaluate objective changes in water content, sebum content, transepidermal water loss (TEWL), and melanin due to breast cancer chemotherapy, and their association with subjective symptoms. Prospective cohort study of 61 patients 18 years of age or older with a postoperative diagnosis of stage I–III breast cancer, who received adjuvant chemotherapy between February and September 2012 at an outpatient breast cancer clinic in Korea. Objective skin parameters, measured using a noninvasive bioengineering device, and patient-reported dryness and dullness were assessed before chemotherapy, after two cycles of chemotherapy, and 1, 3, and 6 months after completion of chemotherapy. Water content (−6.5 %), sebum (−75.5 %), and TEWL (−22.4 %) significantly decreased during chemotherapy compared to pre-chemotherapy levels (all p values <0.001). These parameters were lowest at 1 month after completion of chemotherapy and recovered thereafter but did not return to baseline levels after 6 months of follow-up. Melanin increased during chemotherapy with respect to pre-chemotherapy levels (8.4 %; p < 0.001) but decreased from the first month after completion of chemotherapy through the end of follow-up (−17.1 %; p < 0.001). The patterns of skin changes were similar in patients with or without hormone therapy. Most of patients reported dryness (57.9 %) and dullness (49.1 %) after chemotherapy, and patient-reported dryness was significantly associated with decreased sebum content. Chemotherapy-induced substantial changes in objective skin composition parameters. These changes persisted after 6 months from completion of chemotherapy and were associated with patient-reported symptoms. Additional research is needed to translate these findings into interventions for improving the dermatologic quality of life of breast cancer patients undergoing chemotherapy.


Similar content being viewed by others
Explore related subjects
Discover the latest articles and news from researchers in related subjects, suggested using machine learning.Abbreviations
- T1:
-
Before chemotherapy
- T2:
-
After two cycles of chemotherapy
- T3:
-
1 Month after completion of chemotherapy
- T4:
-
3 Months after completion of chemotherapy
- T5:
-
6 Months after completion of chemotherapy
- CG:
-
Received chemotherapy only group
- CHG:
-
Received chemotherapy and hormone therapy
- AC:
-
Doxorubicin, cyclophosphamide
- FAC:
-
Cyclophosphamide, doxorubicin, fluorouracil
- T:
-
Docetaxel
- TEWL:
-
Transepidermal water loss
References
Stan D, Loprinzi CL, Ruddy KJ (2013) Breast cancer survivorship issues. Hematol/Oncol Clin N Am 27(4):805–827. doi:10.1016/j.hoc.2013.05.005
Griggs JJ, Hawley ST, Graff JJ, Hamilton AS, Jagsi R, Janz NK, Mujahid MS, Friese CR, Salem B, Abrahamse PH, Katz SJ (2012) Factors associated with receipt of breast cancer adjuvant chemotherapy in a diverse population-based sample. J Clin Oncol 30(25):3058–3064
Reich S, Trueb RM (2003) Trichoteiromania. J Deutschen Dermatologischen Gesellschaft 1(1):22–28 (J German Soc Dermatol JDDG)
Katoh M, Kadota M, Nishimura Y (2004) A case of docetaxel-induced erythrodysesthesia. J Dermatol 31(5):403–406
Childress J, Lokich J (2003) Cutaneous hand and foot toxicity associated with cancer chemotherapy. Am J Clin Oncol 26(5):435–436. doi:10.1097/01.coc.0000026486.56886.18
Karam A, Metges JP, Labat JP, Leroy JP, Guillet G (2002) Squamous syringometaplasia associated with docetaxel. Br J Dermatol 146(3):524–525
Chen M, Crowson AN, Woofter M, Luca MB, Magro CM (2004) Docetaxel (taxotere) induced subacute cutaneous lupus erythematosus: report of 4 cases. J Rheumatol 31(4):818–820
Ascherman JA, Knowles SL, Attkiss K (2000) Docetaxel (taxotere) extravasation: a report of five cases with treatment recommendations. Ann Plast Surg 45(4):438–441
Eich D, Scharffetter-Kochanek K, Eich HT, Tantcheva-Poor I, Krieg T (2002) Acral erythrodysesthesia syndrome caused by intravenous infusion of docetaxel in breast cancer. Am J Clin Oncol 25(6):599–602
Chu CY, Yang CH, Yang CY, Hsiao GH, Chiu HC (2000) Fixed erythrodysaesthesia plaque due to intravenous injection of docetaxel. Br J Dermatol 142(4):808–811
Heidary N, Naik H, Burgin S (2008) Chemotherapeutic agents and the skin: an update. J Am Acad Dermatol 58(4):545–570. doi:10.1016/j.jaad.2008.01.001
Gandhi M, Oishi K, Zubal B, Lacouture ME (2010) Unanticipated toxicities from anticancer therapies: survivors’ perspectives. Support Care Cancer 18(11):1461–1468. doi:10.1007/s00520-009-0769-1 (official journal of the Multinational Association of Supportive Care in Cancer)
Haley AC, Calahan C, Gandhi M, West DP, Rademaker A, Lacouture ME (2011) Skin care management in cancer patients: an evaluation of quality of life and tolerability. Support Care Cancer 19(4):545–554. doi:10.1007/s00520-010-0851-8 (official journal of the Multinational Association of Supportive Care in Cancer)
Richardson LC, Wang W, Hartzema AG, Wagner S (2007) The role of health-related quality of life in early discontinuation of chemotherapy for breast cancer. Breast J 13(6):581–587. doi:10.1111/j.1524-4741.2007.00512.x
Ra HS, Shin SJ, Kim JH, Lim H, Cho BC, Roh MR (2013) The impact of dermatological toxicities of anti-cancer therapy on the dermatological quality of life of cancer patients. J Eur Acad Dermatol Venereol 27(1):e53–e59. doi:10.1111/j.1468-3083.2012.04466.x (JEADV)
Pierard GE, Pierard-Franchimont C, Marks R, Paye M, Rogiers V (2000) EEMCO guidance for the in vivo assessment of skin greasiness. The EEMCO Group. Skin Pharmacol Appl Skin Physiol 13(6):372–389
Rogiers V (2001) EEMCO guidance for the assessment of transepidermal water loss in cosmetic sciences. Skin Pharmacol Appl Skin Physiol 14(2):117–128
Hall G, Phillips TJ (2005) Estrogen and skin: the effects of estrogen, menopause, and hormone replacement therapy on the skin. J Am Acad Dermatol 53(4):555–568. doi:10.1016/j.jaad.2004.08.039 (quiz 569–572)
Wines N, Willsteed E (2001) Menopause and the skin. Australas J Dermatol 42(3):148–149 (quiz 159)
Stewart ME, Downing DT (1991) Chemistry and function of mammalian sebaceous lipids. Adv Lipid Res 24:263–301
Fluhr JW, Mao-Qiang M, Brown BE, Wertz PW, Crumrine D, Sundberg JP, Feingold KR, Elias PM (2003) Glycerol regulates stratum corneum hydration in sebaceous gland deficient (asebia) mice. J Invest Dermatol 120(5):728–737. doi:10.1046/j.1523-1747.2003.12134.x
Thody AJ, Shuster S (1989) Control and function of sebaceous glands. Physiol Rev 69(2):383–416
Selleri S, Seltmann H, Gariboldi S, Shirai YF, Balsari A, Zouboulis CC, Rumio C (2006) Doxorubicin-induced alopecia is associated with sebaceous gland degeneration. J Invest Dermatol 126(4):711–720. doi:10.1038/sj.jid.5700175
Alley E, Green R, Schuchter L (2002) Cutaneous toxicities of cancer therapy. Curr Opin Oncol 14(2):212–216
Imokawa G, Hattori M (1985) A possible function of structural lipids in the water-holding properties of the stratum corneum. J Invest Dermatol 84(4):282–284
Perez-Soler R (2003) Can rash associated with HER1/EGFR inhibition be used as a marker of treatment outcome? Oncology 17(11 Suppl 12):23–28
Fluhr JW, Miteva M, Primavera G, Ziemer M, Elsner P, Berardesca E (2007) Functional assessment of a skin care system in patients on chemotherapy. Skin Pharmacol Physiol 20(5):253–259. doi:10.1159/000104423
Proksch E, Brandner JM, Jensen J-M (2008) The skin: an indispensable barrier. Exp Dermatol 17(12):1063–1072. doi:10.1111/j.1600-0625.2008.00786.x
Kobayashi H, Tagami H (2004) Distinct locational differences observable in biophysical functions of the facial skin: with special emphasis on the poor functional properties of the stratum corneum of the perioral region. Int J Cosmet Sci 26(2):91–101. doi:10.1111/j.0412-5463.2004.00208.x
Jensen JM, Forl M, Winoto-Morbach S, Seite S, Schunck M, Proksch E, Schutze S (2005) Acid and neutral sphingomyelinase, ceramide synthase, and acid ceramidase activities in cutaneous aging. Exp Dermatol 14(8):609–618. doi:10.1111/j.0906-6705.2005.00342.x
Rawlings AV, Voegeli R (2013) Stratum corneum proteases and dry skin conditions. Cell Tissue Res 351(2):217–235. doi:10.1007/s00441-012-1501-x
Farage MA, Miller KW, Elsner P, Maibach HI (2013) Characteristics of the aging skin. Adv Wound Care 2(1):5–10. doi:10.1089/wound.2011.0356
Farinelli N, Berardesca E (1995) The skin integument: variation relative to sex, age, race, and body region. In: Serup J, Jemec GBE, Grove GL (eds) Handbook of non-invasive methods and the skin, 2nd edn. CRC, Boca Raton
Hymes SR, Simonton SC, Farmer ER, Beschorner WB, Tutschka PJ, Santos GW (1985) Cutaneous busulfan effect in patients receiving bone-marrow transplantation. J Cutan Pathol 12(2):125–129
Seiberg M (2013) Age-induced hair greying—the multiple effects of oxidative stress. Int J Cosmet Sci 35(6):532–538. doi:10.1111/ics.12090
Chen N, Seiberg M, Lin CB (2006) Cathepsin L2 levels inversely correlate with skin color. J Invest Dermatol 126(10):2345–2347. doi:10.1038/sj.jid.5700409
Thornton MJ (2013) Estrogens and aging skin. Dermato-Endocrinology 5(2):264–270. doi:10.4161/derm.23872
Verdier-Sevrain S, Bonte F, Gilchrest B (2006) Biology of estrogens in skin: implications for skin aging. Exp Dermatol 15(2):83–94. doi:10.1111/j.1600-0625.2005.00377.x
Surazynski A, Jarzabek K, Haczynski J, Laudanski P, Palka J, Wolczynski S (2003) Differential effects of estradiol and raloxifene on collagen biosynthesis in cultured human skin fibroblasts. Int J Mol Med 12(5):803–809
Hardman MJ, Emmerson E, Campbell L, Ashcroft GS (2008) Selective estrogen receptor modulators accelerate cutaneous wound healing in ovariectomized female mice. Endocrinology 149(2):551–557. doi:10.1210/en.2007-1042
Kim SW, Yoon HS (2009) Tamoxifen-induced melasma in a postmenopausal woman. J Eur Acad Dermatol Venereol 23(10):1199–1200. doi:10.1111/j.1468-3083.2009.03113.x (JEADV)
Funding
This work was supported by the research was supported by AMOREPACIFIC and the Korea Breast Cancer Foundation, the Faculty Research Fund, Sungkyunkwan University (2013).
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Conflict of interest
The authors declare that they have no conflict of interest.
Additional information
Dong-Youn Lee and Juhee Cho contributed equally to this study.
Electronic supplementary material
Below is the link to the electronic supplementary material.
Figure S1 (TIFF 58 kb)
Trajectories of water content (a), sebum content (b), transepidermal water loss (TEWL) (c), and melanin index (d) on the cheek according to the type of chemotherapy before, after two cycles of chemotherapy, and after completion of chemotherapy. AC doxorubicin and cyclophosphamide (n = 16); FAC cyclophosphamide, doxorubicin, and fluorouracil (n = 16); AC + T doxorubicin, cyclophosphamide, and docetaxel (n = 29). Hormone therapy was received by 87.5, 50, and 72.4% of those receiving AC, FAC, and AC + T, respectively Differences between the slopes in the three groups were not statistically significant. The chemotherapy regimen included doxorubicin, cyclophosphamide, cyclophosphamide, doxorubicin, fluorouracil, and taxotere. T1 before chemotherapy, T2 after two cycles of chemotherapy, T3 1 month after completion of chemotherapy, T4 3 months after completion of chemotherapy, T5 6 months after completion of chemotherapy
Rights and permissions
About this article
Cite this article
Kang, D., Kim, IR., Im, Y.H. et al. Quantitative changes in skin composition parameters due to chemotherapy in breast cancer patients: a cohort study. Breast Cancer Res Treat 152, 675–682 (2015). https://doi.org/10.1007/s10549-015-3502-4
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10549-015-3502-4