Breast cancer skin recurrence: a comprehensive review on pathogenesis, treatment, and prognosis

Georgios Pechlivanides, Vassilios Kalles, Georgios Boutsikos, Lazaros Papadopoulos


The manifestation of breast cancer recurrence in the form of skin lesions has always been a frustration for both the oncologist and the breast surgeon. Surgeons are asked to treat a recurrent disease that is yet unclear whether it represents disseminated or local disease. Cancer cells are found both in the lymphatics as well as the blood vessels, but, on the other hand, skin recurrence usually does not respond well to the current forms of systemic treatment, and it often needs some form of local treatment for symptom control.


breast cancer, cutaneous metastases, skin metastases


Collier de AH, Busam K, Salob S. Cutaneous metastasis of osteosarcoma. J Am Acad Dermatol 2003; 49: 757.

Hussein MR. Skin metastasis: a pathologist's perspective. J Cutan Parhol 2010;37(9): e1-2.

Arce FP, Pinto J,Portero I, Echevarria S,Val-Bernal JF. Cutaneous metastases as initial manifestation of dedifferentiated chondrosarcoma of bone. An autopsy case with review of the literature. J Cutan Pathol 2000; 27: 262.

Metastatic cutaneous breast carcinoma: A case report and review of the literature. Can J Plast Surg 2009; 17(1):25-7.

Krathen RA, Orego IF, Rosen T. Cutaneous metastasis: a meta-analysis of data. South Med J 2003;96(2):164-7.

Varol U, Yildiz I, Alacacioglu A, Uslu R. Anticancer therapy for breast cancer patients with skin metastases refractory to conventional treatments. Asian Pac J Cancer Prev. 2014;15(4):1885-7.

Hu SC, Chen G, Wu C, et al. Rates of cutaneous metastases from different internal malignancies: experience from a Taiwanese medical center. J Am Acad Dermatol. 2009; 60:379-387.

Saeed S, Keehn CA, Morgan MB. Cutaneous metastasis: a clinical, pathological, and immunohistochemical appraisal. J Cutan Pathol 2004; 31: 419

Nguyen TH. Mechanisms of metastasis. Clin Dermatol 2004; 22: 209.

Hussein MR. Alterations of p53, Bcl-2, and hMSH2 protein expression in the cirrhotic, macroregenerative, dysplastic nodules and hepatocellular carcinomas in Upper Egypt. Liver Int 2004; 24: 552.

Raguenez G, Blanc E, Benard J. Metastatic potential: a generic characteristic of the primary tumor. Bull Cancer 2004; 91: 129.

Geiger TR, Peeper DS. Metastasis mechanisms. Biochim Biophys Acta 2009; 1796: 293.

Bohle AS, Kalthoff H. Molecular mechanisms of tumor metastasis and angiogenesis. Langenbecks Arch Surg 1999; 384: 133.

Bogenrieder T, Herlyn M. Axis of evil: molecular mechanisms of cancer metastasis. Oncogene 2003; 22: 6524.

Jung Sun Lee, Woo Gyeong Kim. Cutaneous metastases of breast cancer during adjuvant chemotherapy correlates with increasing CD44+/CD24− and ALDH-1 expression: a case report and literature review. Stem Cell Investig 2018; 5:7.

Kauffman CL, Sina B. Metastatic inflammatory carcinoma of the rectum: tumor spread by three routes. Am J Dermatopathol. 1997;19(5):528–32.

Dehal A, Patel S, Kim S, Shapera E, Hussain F. Cutaneous Metastasis of Rectal Cancer: A Case Report and Literature Review. Perm J 2016 ;20(1):74-78/

Yun SJ, Park HY, Lee JS, Park MH, Lee JB, Won YH. Clinicopathological correlation of cutaneous metastatic breast carcinoma using lymphatic and vascular markers: lymphatics are mainly involved in cutaneous metastasis. Clin Exp Dermatol 2012 Oct; 37(7):744-8.

Cohen PR, Prieto VG. Radiation port xanthogranuloma: Solitary xanthogranuloma occurring within the irradiated skin of a breast cancer patient-report and review of cutaneous neoplasms developing at the site of radiotherapy. J Cutan Pathol. 2010;37:891–4.

Diehl LF, Hurwitz MA, Johnson SA, Butler WM, Taylor HG. Skin metastases confined to a field of previous irradiation. Report of two cases and review of the literature. Cancer 1984;53:1864-8.

Hoyt BS, Cohen PR. Radiation port cutaneous metastases: Reports of two patients whose recurrent visceral cancers presented as skin lesions at the site of previous radiation and literature review. Indian J Dermatol 2014;59:176-81.

Nashan D, Meiss F, Braun-Falco M, Reichenberger S. Cutaneous metastases from internal malignancies. Dermatol Ther. 2010;23:567–80.

Wolf R, Brenner S, Ruocco V, Filioli FG. Isotopic response. Int J Dermatol 1995;34:341-8.

Shurman D, Reich HL, James WD. Lichen planus confined to a radiation field: The "isoradiotopic" response. J Am Acad Dermatol 2004;50:482-3.

Diehl LF, Hurwitz MA, Johnson SA, Butler WM, Taylor HG. Skin metastases confined to a field of previous irradiation. Report of two cases and review of the literature. Cancer 1984;53:1864-8.

Ruocco E, Di Maio R, Caccavale S, Siano M, Lo Schiavo A. Radiation dermatitis, burns, and recall phenomena: Meaningful instances of immunocompromised district. Clin Dermatol. 2014;32(5):660-9.

Smith KJ, Yeager J, Skelton HG. Localized scleroderma in breast cancer patients treated with supervoltage external beam radiation: Radiation port scleroderma. J Am Acad Dermatol 1997;37:806-8.

Hu SC, Chen GS, Lu YW, Wu CS, Lan CC. Cutaneous metastases from different internal malignancies: a clinical and prognostic appraisal. J Eur Acad Dermatol Venereol. 2008; 22(6) :735-40.

Lookingbill DP, Spangler N, Helm KF. Cutaneous matastases in patients with metastatic cascinoma: a retrospective study of 4020 patients. J Am Acad Dermatol. 1993;29(2,part1):228-236.

Schwartz RA, Wiederkehr M, Lambert WC. Secondary mucinous carcinoma of the skin: metastatic breast cancer. Dermatol Surg. 2004;30:234-5.

Nashan D, Muller ML, Braun-Falco M, Reichenberger S, Szeimies RM, Bruckner – Tuderman L. Cutaneous metastases of visceral tumours: a review. J Cancer Res Clin Oncol 2009;135(1):1-14.

Saeed S, Keehn CA, Morgan MB. Cutaneous metastasis: a clinical, pathological, and immunohistochemical appraisal. J Cutan Pathol 2004; 31: 419

Brownstein MH,Helwig EB. Patterns of cutaneous metastasis. Arch Dermatol 1972; 105: 862.

Bauza A, Redondo P, Idoate MA. Cutaneous zosteriform squamous cell carcinoma metastasis arising in an immunocompetent patient. Clin Exp Dermatol 2002; 27: 199.

Yaghoobi R, Mostoufi NE, Sina N. Zosteriform Skin Metastases from Breast Cancer Iran J Med Sci 2003; 28(4):203-205.

Werling RW, Yaziji H, Bacchi CE, Gown AM. CDX2, a highly sensitive and specific marker of adenocarcinomas of intestinal origin: an immunohistochemical survey of 476 primary and metastatic carcinomas. Am J Surg Pathol 2003; 27: 303.

Mosnier JF, Kandel C, Cazals-Hatem D, et al. N-cadherin serves as diagnostic biomarker in intrahepatic and perihilar cholangiocarcinomas. Mod Pathol 2009; 22: 182.

Matsuoka K, Ohsumi S, Takashima S, Saeki T, Aogi K, Mandai K. Occult breast carcinoma presenting with axillary lymph node metastases: follow-up of eleven patients. Breast Cancer 2003; 10: 330.

Green AR, Young P, Krivinskas S, et al. The expression of ERalpha, ERbeta and PR in lobular carcinoma in situ of the breast determined using laser microdissection and real-time PCR. Histopathology 2009; 54: 419.

Aloi F, Solaroli C, Paradiso M, Formiconi A. Inflammatory type cutaneous metastasis of bladder neoplasm: erysipeloid carcinoma. Minerva Urol Nefrol 1998; 50: 205.

Copeman PW, Farthing CF, Leader M. Cutaneous metastasis (cancer en cuirasse and carcinoma erysipelatoides): a noninvasive search for the primary cancer using microscopical techniques on urine and skin. J R Soc Med 1985; 78(Suppl. 11): 43.

Fusade T, Boullie MC, Thomine E, Lauret PH. Cutaneous metastasis disclosing primary angiosarcoma of the aorta. Ann Dermatol Venereol 1991; 118: 701.

Baum EM, Omura EF, Payne RR, Little WP. Alopecia neoplastica–a rare form of cutaneous metastasis. J Am Acad Dermatol 1981; 4: 688.

Damin DC, Lazzaron AR, Tarta C, Cartel A, Rosito MA. Massive zosteriform cutaneous metastasis from rectal carcinoma. Tech Coloproctol 2003; 7: 105.

Marneros AG, Blanco F, Husain S, Silvers DN, Grossman ME. Classification of cutaneous intravascular breast cancer metastases based on immunolabeling for blood and lymph vessels. J Am Acad Dermatol. 2009 Apr;60(4):633-8.

Schoenlaub P, Sarraux A, Grosshans E, Heid E, Cribier B. Survival after cutaneous metastasis: a study of 200 cases. Ann Dermatol Venereol 2001; 128: 1310.

Gonzalez-Angulo AM, Morales-Vasquez F, Hortobagyi GN. Overview of resistance to systemic therapy in patients with breast cancer. Adv Exp Med Biol. 2007; 608:1-22.

Kalmykow B1, Walker S. Cutaneous metastases in breast cancer. Clin J Oncol Nurs. 2011 Feb;15(1):99-101.

Conlin AK, Seidman AD. Beyond cytotoxic chemotherapy for the first-line treatment of HER2-negative, hormone-insensitive metastatic breast cancer: current status and future opportunities. Clin Breast Cancer 2008; 8(3):215-23.

Coşkun U, Gunel N, Yamac D, Altinova AE. Effect of cisplatin on skin metastasis in breast cancer patients. Onkologie 2011, 24, 576-9.

Stein ME, Quigley MM, Gershuny A, Zaidan J, Danieli NS. Long-standing complete remission following mitomycin-C/vinblastine chemotherapy for cutaneous and lymph node metastases from breast cancer resistant to multiple chemotherapy and hormonal lines and extensive radiotherapy: an unusual case. J BUON. 2005 Jul-Sep;10(3):401-3.

Eisenhauer E, Therasse P, Bogaerts J, et al. New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer. 2009;45:228-247.

Kong JH, Park YH, Kim JA, Kim JH, Yun J, Sun JM, Won YW, Lee S, Kim ST, Cho EY, Ahn JS, Im YH. Patterns of skin and soft tissue metastases from breast cancer according to subtypes: relationship between EGFR overexpression and skin manifestations. Oncology 2011, 81, 55-62.

Ihnen M, Kilic E, Köhler N, Loning T, Witzel I, Hagel C, Holler S, Kersten JF, Muller V, Janicke F, Midle-Langosch K. Protein expression analysis of ALCAM and CEACAM6 in breast cancer metastases reveals significantly increased ALCAM expression in metastases of the skin. J Clin Pathol 2011, 64, 146-52.

Wollina U. Cetuximab in non-melanoma skin cancer. Expert Opin Biol Ther 2012, 12, 949-56.

Gholam D, Chebib A, Hauteville D, Bralet MP, Jasmin C . Combined paclitaxel and cetuximab achieved a major response on the skin metastases of a patient with epidermal growth factor receptor-positive, estrogen receptor-negative, progesterone receptor-negative and human epidermal growth factor receptor-2-negative (triple-negative) breast cancer. Anticancer Drugs 2007, 18, 835-7.

Cottu PH, Fourchotte V, Vincent-Salomon A, Kriegel I, Fromantin I. Necrosis in breast cancer patients with skin metastases receiving bevacizumab-based therapy. J Wound Care 2011, 20, 403-4.

Insa A, Lluch A, Prosper F, et al. Prognostic factors predicting survival from first recurrence in patients with metastatic breast cancer: analysis of 439 patients. Breast Cancer Res Treat. 1999;56:67-78.

Zagar TM, Higgins KA, Miles EF, et al. Durable palliation of breast cancer chest wall recurrence with radiation therapy, hyperthermia, and chemotherapy. Radiother Oncol. 2010;97: 535–40.

Oldenborg S, Van Os RM, Van Rij CM, et al. Elective re-irradiation and hyperthermia following resection of persistent locoregional recurrent breast cancer: a retrospective study. Int J Hyperthermia. 2010; 26:136–44.

Spratt DE, Gordon Spratt EA, Wu S, et al. Efficacy of skin directed therapy for cutaneous metastases from advanced cancer: a meta-analysis. J Clin Oncol. 2014; 32: 3144–55.

Guarneri V, Conte P. Metastatic breast cancer: therapeutic options according to molecular subtypes and prior adjuvant therapy. Oncologist. 2009; 14:645–56.

Leonard R, Hardy J, van Tienhoven G, et al. Randomized, double-blind, placebo-controlled, multicenter trial of 6 % miltefosine solution, a topical chemotherapy in cutaneous metastases from breast cancer. J Clin Oncol. 2001; 21:4150–9.

Mir LM, Orlowski S. Mechanisms of electrochemotherapy. Adv Drug Deliv Rev. 1999; 35:107–18.

Mali B, Jarm T, Snoj M, et al. Antitumor effectiveness of electrochemotherpay: a systematic review and meta-analysis. Eur J Surg Oncol. 2013; 39:4–16.

Cabula C, Campana LG, Grilz G, Galuppo S, Bussone R, De Meo L, Bonadies A, Curatolo P, De Laurentis M, Renna M, Valpione S, Fabrizio T, Solari N, Guida M, Santoriello A, D'Aiuto M, Agrasti R. Electrochemotherapy in the Treatment of Cutaneous Metastases from Breast Cancer: A Multicenter Cohort Analysis. Ann Surg Oncol 2015; 22: S442–S450.

Campana LG, Campana LG, Teastori A, Curatolo P, Quaglino P, Mocellin S, Framarini M, Borgognoni L, Ascierto PA, Mozzilo N, Guida M, Bucher S, Roturno R, Marenco F, De Salvo GL, De Paoli A, Rossi CR, Bonadies A. Treatment efficacy with electrochemotherapy: A multi-institutional prospective observational study on 376 patients with superficial tumors. Eur J Surg Oncol 2016 Jun 29. pii: S0748-7983(16)30606-0. doi: 10.1016/j.ejso.2016.06.399.

Fayter D, Corbett M, Heirs M, Fox D, Eastwood A. A systematic review of photodynamic therapy in the treatment of pre-cancerous skin conditions, Barrett's oesophagus and cancers of the biliary tract, brain, head and neck, lung, oesophagus and skin. Health Technol Assess. 2010 Jul;14(37):1-288.

Leonard R1, Hardy J, van Tienhoven G, Houston S, Simmonds P, David M, Mansi J. Randomized, double-blind, placebo-controlled, multicenter trial of 6% miltefosine solution, a topical chemotherapy in cutaneous metastases from breast cancer. J Clin Oncol. 2001 ;19(21):4150-9.

Henriques L, Palumbo M, Guay MP, Bahoric B, Basik M, Kavan P, Batist G Imiquimod in the treatment of breast cancer skin metastasis. J Clin Oncol. 2014;32(8):e22-5.

Dong J., Liu P., Zhang A., Xu L.X. Immunological response induced by alternated cooling and heating of breast tumor. Conf Proc IEEE Eng Med Biol Soc.;2007:1491–1494.

Hachisuka J, Doi K, Furue M. Combination cryosurgery with hyperthermia in the management of skin metastasis from breast cancer: A case report. Int J Surg Case Rep 2012;3: 68-9.

Triozzi PL, Allen KO, Carlisle RR, Craig M, LoBuglio AF, Conry RM. Phase I study of the intratumoral administration of recombinant canarypox viruses expressing B7.1 and interleukin 12 in patients with metastatic melanoma. Clin Cancer Res 2005;11:4168-4175.

Dummer R, Rochlitz C, Velu T, Acres B, Limacher JM, Bleuzen P, Lacoste G, Slos P, Romero P, Urosevic M. Intralesional adenovirus-mediated interleukin-2 gene transfer for advanced solid cancers and melanoma. Mol Ther 2008;16:985-994.

Hofmann MA, Kors C, Audring H, Walden P, Sterry W, Trefzer U. Phase 1 evaluation of intralesionally injected TLR9-agonist PF-3512676 in patients with basal cell carcinoma or metastatic melanoma. J Immunother 2008;31:520-527.

Weide B, Derhovanessian E, Pflugfelder A, Leiter U, Meier F, Bauer J, Schmidt D, Radny P, Pföhler C, Garbe C. High response rate after intratumoral treatment with interleukin-2: Results from a phase 2 study in 51 patients with metastasized melanoma. Cancer 2010;116:4139-4146.

Moore S. Cutaneous metastatic breast cancer. Clin J Oncol Nurs. 2002;6(5):255-60.

Le Scodan R, Stevens D, Brain E, et al. Breast cancer with synchronous metastases: survival impact of exclusive locoregional radiotherapy. J Clin Oncol. 2009;27(9):1375–1381.

Menendez PR, Roth BM, Pereira MD, et al: BNCT for skin melanoma in extremities: Updated Argentine clinical results. Appl Radiat Isot 2009;67:S50- S53.

Overgaard J, von der Maase H, Overgaard M: A randomized study comparing two high-dose per fraction radiation schedules in recurrent or metastatic malignant melanoma. Int J Radiat Oncol Biol Phys 1985; 11:1837-1839.



  • There are currently no refbacks.

Creative Commons License
This work is licensed under a Creative Commons Attribution 3.0 License.