Basal-Cell Carcinoma

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Feb 16, 2006 - Basal-Cell Carcinoma. To the Editor: The excellent review by Rubin et al. of basal-cell carcinoma (Nov. 24 issue)1 con- siders the genital area ...
correspondence

in randomized trials. Despite the conclusions of based on empirical information on survival acBerry et al., the situation is still partly contentious. cording to tumor stage, hormonal status, method of detection, and treatment. Regarding women Michael W. Retsky, Ph.D. whose breast cancer is detected in their 40s: we Harvard Medical School Boston, MA 02115 did not address this issue separately, but we plan [email protected] to do so in future work. Romano Demicheli, M.D., Ph.D. Dr. Smith comments on the lack of additivIstituto Nazionale Tumori ity in Table 3. These are not errors. We indicated 20137 Milan, Italy in the article that “the combination of screening William J.M. Hrushesky, M.D. and adjuvant therapy reduced the rate of death WJB Dorn Veterans Affairs Medical Center by slightly less than the sum of the contributions Columbia, SC 29209 from screening and adjuvant therapy alone.” The 1. Demicheli R, Terenziani M, Valagussa P, Moliterni A, Zam- approximate additivity of screening and adjuvant betti, Bonadonna G. Local recurrences following mastectomy: support for the concept of tumour dormancy. J Natl Cancer Inst therapy is interesting, because it means that we 1994;86:45-8. concluded there was little synergism between the 2. Retsky M, Demicheli R, Hrushesky WJM. Does surgery induce two interventions. angiogenesis in breast cancer? Indirect evidence from relapse patWe agree with Dr. Gøtzsche that our study tern and mammography paradox. Int J Surgery 2005;3:179-87. 3. Jatoi I, Tsimelzon A, Weiss H, Clark GM, Hilsenbeck SG. should be repeated in other countries. We also Hazard rates of recurrence following diagnosis of primary breast agree that there is some randomness — we used cancer. Breast Cancer Res Treat 2005;89:173-8. 4. Jerez JM, Franco L, Alba E, et al. Improvement of breast cancer the term “uncertainty” — associated with our conrelapse prediction in high risk intervals using artificial neural clusion that there was a 15 percent reduction asnetworks. Breast Cancer Res Treat 2005;94:265-72. sociated with screening in the United States. As to whether 15 percent is a “random high,” we point The authors reply: We agree with Dr. Baker out that it was the median of seven estimates that the commonality of our conclusions is driv- ranging from 7.5 percent to 22.7 percent. With regard to the comments of Dr. Baglioni: en partly by the availability of common data our goal was to address the relative contributions sources. However, we had a wide variety of types of adjuvant therapy and screening to the observed of information available, and each of us selected decrease in breast-cancer mortality in the United data relevant to our particular models. Not all of us used the same data, and not all of us used the States and not to address an individual woman’s available data in the same way. Regarding the decision process. We agree with Dr. Baglioni that provision of critical details, additional informa- absolute survival benefit is the appropriate contion is available in the Supplementary Appendix sideration for individual decision making. (available with the full text of our article at www. Donald A. Berry, Ph.D. nejm.org) and on our Web site (cisnet.cancer.gov). M.D. Anderson Cancer Center Still more descriptions of each model will be pro- Houston, TX 77030 [email protected] vided in future publications. In reply to Dr. Retsky and colleagues: it is not Sylvia K. Plevritis, Ph.D. true that all our models assumed continuous tu- Stanford University mor growth over time. Some models specifically Stanford, CA 94305 allowed for tumors — both in situ and invasive Dennis G. Fryback, Ph.D. — that were not lethal. Moreover, one model did University of Wisconsin–Madison not consider tumor growth at all but, instead, was Madison, WI 53706

Basal-Cell Carcinoma To the Editor: The excellent review by Rubin et cell carcinomas. In our view, this site, especially al. of basal-cell carcinoma (Nov. 24 issue)1 con- the vulva, is neither unusual nor random. Like siders the genital area an unusual site for basal- melanoma,2 even basal-cell carcinomas appear

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in sun-shielded areas such as the vulva, challenging the conventional knowledge that associates these cancers with ultraviolet radiation. Vulvar basal-cell carcinoma typically includes poor pigmentation and, often, a clinical appearance that mimics eczema or psoriasis.3 The dominant symptom, itching, often induces both patients and doctors to dismiss the condition as a simple irritation or intertrigo. Thus, inappropriate treatment for inflammatory or infectious dermatosis often delays the correct diagnosis. Consequently, the neoplasm grows (average size in our report,3 2.1 cm; ulceration occurred in 28 percent of cases, 25 percent with neoplastic involvement of excision margins), which means a more invasive excision and more discomfort on the part of the patient, with obvious negative therapeutic (and psychological) repercussions.3 General practitioners and gynecologists need to be aware that these neoplasms can occur in areas normally protected from ultraviolet radiation and that they can have worse outcomes than basal-cell carcinomas appearing at other sites. Vincenzo De Giorgi, M.D. Daniela Massi, M.D. Torello Lotti, M.D. University of Florence 50121 Florence, Italy [email protected] 1. Rubin AI, Chen EH, Ratner D. Basal-cell carcinoma. N Engl

J Med 2005;353:2262-9. 2. de Giorgi V, Massi D, Salvini C, Mannone F, Cattaneo A, Carli P. Thin melanoma of the vulva: a clinical, dermoscopicpathologic case study. Arch Dermatol 2005;141:1046-7. 3. de Giorgi V, Salvini C, Massi D, Raspollini MR, Carli P. Vulvar basal cell carcinoma: retrospective study and review of literature. Gynecol Oncol 2005;97:192-4.

To the Editor: In discussing different nonsurgical approaches to the treatment of basal-cell carcinoma, Rubin and colleagues highlight the efficacy of topical treatment methods, radiotherapy, and photodynamic therapy for localized disease. However, treatment remains unsatisfactory for locally destructive, potentially metastatic basal-cell carcinomas with an aggressive histologic growth pattern and a proximity to vital structures. Advances in the understanding of the aberrant signaling pathways in various solid tumors have revealed a pivotal role for the epidermal growth

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factor receptor (EGFR) and have led to the development of monoclonal antibodies (e.g., cetuximab) and specific tyrosine kinase inhibitors as EGFRtargeting agents. Cetuximab has efficacy in metastatic colorectal cancer that expresses EGFR and is refractory to irinotecan.1 In the epidermis, EGFR is predominantly expressed in the basal layer,2 with increased expression in basal-cell carcinoma relative to normal skin.3 Constitutive expression of the sonic hedgehog pathway in the cells of basal-cell carcinoma is associated with increased levels of phosphorylated EGFR, and sonic-hedgehog–induced cellular matrix infiltration is an EGFR-dependent process.4 Thus, there is a rationale for evaluating anti-EGFR therapies in advanced basal-cell carcinoma. Hansgeorg Mueller, M.D. Klaus Eisendle, M.D., Ph.D. Peter Fritsch, M.D. Medical University Innsbruck 6020 Innsbruck, Austria [email protected] 1. Cunningham D, Humblet Y, Siena S, et al. Cetuximab mono-

therapy and cetuximab plus irinotecan in irinotecan-refractory metastatic colorectal cancer. N Engl J Med 2004;351:337-45. 2. Nanney LB, Magid M, Stoscheck CM, King LE Jr. Comparison of epidermal growth factor binding and receptor distribution in normal human epidermis and epidermal appendages. J Invest Dermatol 1984;83:385-93. 3. Krahn G, Leiter U, Kaskel P, et al. Coexpression patterns of EGFR, HER2, HER3 and HER4 in non-melanoma skin cancer. Eur J Cancer 2001;37:251-9. 4. Bigelow RL, Jen EY, Delehedde M, Chari NS, McDonnell TJ. Sonic hedgehog induces epidermal growth factor dependent matrix infiltration in HaCaT keratinocytes. J Invest Dermatol 2005;124:457-65.

The authors reply: We agree with Dr. Mueller and colleagues that at this time, high-risk basalcell carcinoma is not optimally treated with nonsurgical methods. The potential role of a new mechanism-based therapy dependent on the actions of EGFR would be worth investigating further. Such a therapy could be used as either a primary or an adjunctive treatment for basal-cell carcinoma in a variety of clinical situations. Dr. De Giorgi and colleagues provide useful information regarding vulvar basal-cell carcinoma. The development of basal-cell carcinoma in sun-protected sites such as the genitalia demonstrates that the induction of this tumor is multifactorial. The relative importance of factors other

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than exposure to ultraviolet radiation may be elucidated by further study of the subgroup of patients with such cancers. However, the development of basal-cell carcinoma in the genital area is an unusual event. Gibson and Ahmed reported a series of 51 basalcell carcinomas in the perianal and genital regions, which made up 0.27 percent of basal-cell carcinomas at the authors’ institution.1 Furthermore, in the recent article by De Giorgi et al., the 63 cases of vulvar basal-cell carcinoma accounted for only 1.75 percent of the 3604 cases of basal-cell carcinomas at their institution during the study period.2 De Giorgi and colleagues correctly state that vulvar basal-cell carcinoma can mimic eczema or psoriasis, as can occur in cases of superficial basal-cell carcinomas at other body

sites as well. In general, patients with cutaneous diseases that fail to respond to initial therapies benefit from a skin biopsy to help confirm a suspected diagnosis or to exclude the possibility of a neoplastic process such as basal-cell carcinoma. Adam I. Rubin, M.D. Elbert H. Chen, M.D. Désirée Ratner, M.D. Columbia University College of Physicians and Surgeons New York, NY 10032 [email protected] 1. Gibson GE, Ahmed I. Perianal and genital basal cell carci-

noma: a clinicopathologic review of 51 cases. J Am Acad Dermatol 2001;45:68-71. 2. de Giorgi V, Salvini C, Massi D, Raspollini MR, Carli P. Vulvar basal cell carcinoma: retrospective study and review of literature. Gynecol Oncol 2005;97:192-4.

Newly Diagnosed HIV Infection To the Editor: In his article on the management of newly diagnosed human immunodeficiency virus (HIV) infection (Oct. 20 issue),1 Hammer did not specifically recommend screening for gonorrhea and chlamydia. These often asymptomatic infections can cause disease, increase the transmissibility of HIV,2 and result in elevated plasma levels of HIV type 1 (HIV-1) RNA and decreased CD4 cell counts.3,4 In a study of early HIV infection, we screened all patients with newly diagnosed HIV for pharyngeal, urethral, and rectal gonorrhea and chlamydia with the use of nucleic acid amplification (BD ProbeTec ET, BD Diagnostic Systems; APTIMA Combo 2 assay, Gen-Probe). Among 52 patients, 98 percent were men who have sex with men; the median age was 36 years (interquartile range, 30 to 40), the median plasma HIV-1 RNA level was 22,097 copies per milliliter (interquartile range, 3306 to 168,730), and the median number of sex partners during the six months before testing was three (interquartile range, two to four). We detected rectal gonorrhea in six patients (12 percent), rectal chlamydia in five (10 percent), pharyngeal gonorrhea in four (8 percent), and urethral gonorrhea in one (2 percent). Overall, we diagnosed one or more sexually transmitted diseases in 12 patients (23 percent).

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U.S. federal guidelines recommend periodic screening for gonorrhea and chlamydia in HIVinfected persons.5 The high prevalence of gonorrhea and chlamydia in our study supports the use of comprehensive screening for patients with newly diagnosed HIV infection as well. Peter V. Chin-Hong, M.D. Frederick M. Hecht, M.D. Jeffrey D. Klausner, M.D., M.P.H. University of California at San Francisco San Francisco, CA 94143 [email protected] Dr. Hecht reports having received lecture fees from Gen-Probe and Abbott; and Dr. Klausner, lecture fees from King Pharmaceuticals and grant support from Pfizer. 1. Hammer SM. Management of newly diagnosed HIV infec-

tion. N Engl J Med 2005;353:1702-10. 2. Wasserheit JN. Epidemiological synergy: interrelationships between human immunodeficiency virus infection and other sexually transmitted diseases. Sex Transm Dis 1992;19:61-77. 3. Buchacz K, Patel P, Taylor M, et al. Syphilis increases HIV viral load and decreases CD4 cell counts in HIV-infected patients with new syphilis infections. AIDS 2004;18:2075-9. 4. Sadiq ST, Taylor S, Copas AJ, et al. The effects of urethritis on seminal plasma HIV-1 RNA loads in homosexual men not receiving antiretroviral therapy. Sex Transm Infect 2005;81:120-3. 5. Incorporating HIV prevention into the medical care of persons living with HIV: recommendations of CDC, the Health Resources and Services Administration, the National Institutes of Health, and the HIV Medicine Association of the Infectious Diseases Society of America. MMWR Recomm Rep 2003;52(RR-12): 1-24. [Erratum, MMWR Morb Mortal Wkly Rep 2004;53:744.]

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