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Clinical Oncology 26 (2014) 174e177

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Clinical Oncology

journal homepage: www.cl in icaloncologyonl ine.net

Letters

Clinical Outcome of HER2-positive Breast Cancer Patients after Failureon Adjuvant Trastuzumab: The Potential of the Time to Relapse

Sir d We read with great interest the paper by Langet al. [1]. The authors reported that trastuzumab combinedwith taxane is an effective and well-tolerated first-linetreatment for patients relapsing on trastuzumab-basedadjuvant therapy. We provide additional data suggestingthat the timing of relapse matters in the management ofthese patients. Among cases treated in the first quarter of2013 at INT, Milan, relapses occurred during (early) or after(late) adjuvant therapy in 12 (30%) and 28 (70%) patients.Early and late relapses shared a similar distribution ofhormone receptor-positive and -negative status (35% versus25%, P ¼ 0.73). Early relapses were less likely to affect lung,bone and multiple metastatic sites; liver was involved in42 and 29% of early and late relapses, respectively (P¼ 0.48).Trastuzumab and tyrosine kinase inhibitors were pre-scribed in 78 and 18% of cases. At a median follow-up of 21.3(0.6e98.6) months, the median time-to-progression (TTP)was 12.7 (95% confidence interval: 9.0e15) months.Consistent with the data by Lang et al. [1] our series sup-ports the use of anti-HER2 beyond progression to adjuvanttherapy. Notwithstanding the above, early relapses had aworse TTP than late relapses, 9.2 (95% confidence interval:3.9e13.3) versus 15 (95% confidence interval: 9.1e27.9)months; P ¼ 0.065. Conversely, Lang et al. [1] reported nodifferencewith respect to the timing from adjuvant therapy.However, the study by Lang et al. [1] recruited patients re-lapsing �6 months after the last adjuvant therapy dose. Itseems to us that early relapses are a poorly studied popu-lation [2,3], yet we found a significant correlation between

the timing from adjuvant therapy and TTP, with a risk ofprogression to first-line reduced by 4% for each additionalrelapse-free month (hazard ratio 0.96,95% confidence in-terval 0.93e0.99, P ¼ 0.009). We kindly ask Lang et al. tocomment on these data and suggest a possible therapeuticstrategy for patients with recurrent breast cancer duringadjuvant trastuzumab.

S. Di Cosimo*a, D. Serpico*a, L. Porcuy, L. Molino*,G. Fanetti*, V. Torriy, F. de Braud**Department of Medical Oncology,

Fondazione IRCCS Istituto Nazionale Tumori, Milan, ItalyyDepartment of Oncology, Istituto di Ricerche Farmacologiche

“Mario Negri” e IRCCS, Milan, Italy

a Authors contributed equally to this work.

References

[1] Lang I, Bell R, Feng FY, et al. Trastuzumab retreatment afterrelapse on adjuvant trastuzumab therapy for humanepidermal growth factor receptor 2-positive breast cancer:final results of the Retreatment after Herceptin Adjuvant Trial.Clin Oncol 2013;26(2):81e89.

[2] Baselga J, Cort�es J, Kim SB, et al, for the CLEOPATRA StudyGroup. Pertuzumab plus trastuzumab plus docetaxel formetastatic breast cancer. N Engl J Med 2012;366:109e119.

[3] Verma S, Miles D, Gianni L, et al, for the EMILIA Study Group.Trastuzumab emtansine for HER2-positive advanced breastcancer. N Engl J Med 2012;367:1783e1791.

� 2013 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved

http://dx.doi.org/10.1016/j.clon.2013.11.028

Inadequate Family History Assessment by Oncologists is an ImportantPhysician Barrier to Referral for Hereditary Breast Cancer Evaluation

Sir d Enhanced surveillance and interventional mea-sures have been shown to improve outcome in hereditarybreast-ovarian cancer syndrome (HBOC), but referral ofhigh-risk patients for genetic counselling remains poorworldwide [1,2]. Apart from patient barriers such as cost,poor awareness and worry of potential repercussions,physician barriers play a contributory role [3e5].

We retrospectively reviewed 6207 genograms con-structed at our centre between 2001 and 2012 andidentified 615 families estimated to harbour more than a10% chance of carrying a BRCA1/2 mutation based onfamily or personal cancer history. In total, 506 hadmedical records available for a review of the quality offamily history assessment by the oncologist, physician

Table 1Factors associated with the likelihood of physician suspicion ofhereditary breast-ovarian cancer syndrome (n ¼ 506)

Taking a good family history Proportion of physician-suspected hereditarybreast-ovarian cancersyndrome, n (%)

Yes (n ¼ 274) 127 (46.4) P [ 0.001No (n ¼ 232) 74 (31.9)Constructing a genogramYes (n ¼ 227) 100 (44.1) P ¼ 0.073No (n ¼ 279) 101 (36.2)Taking a smoking anddrinking history

Yes (n ¼ 330) 132 (40) P ¼ 0.862No (n ¼ 176) 69 (39.2)Patient risk categoriesYoung-onset cancer (n ¼ 343) 156 (45.5) P [ 0.001Breast cancer families (n ¼ 91) 21 (23.1)Breast and ovarian cancerfamilies (n ¼ 50)

17 (34)

Others (n ¼ 22) 7 (31.8)

P-values that are statistically significant (<0.05) are indicated inbold.

Letters / Clinical Oncology 26 (2014) 174e177 175

suspicion of HBOC and referral or not to the cancergenetics clinic.

A good family history that spanned at least threeconsecutive generations was documented in just over halfthe population and was taken less frequently than smokingand drinking history (54.2% versus 65.2%; P < 0.001). HBOCwas correctly suspected in 39.7% (201/506) of cases, ofwhich most (158/201, 78.6%) were referred for geneticevaluation. On univariate analysis, taking a good familyhistory and young-onset cancer increased the likelihood ofphysician suspicion (Table 1). Of the 348/506 cases thatwere not referred, an inadequate family history assessmentwas the most common reason (n ¼ 158, 45.4%), followed bya lack of suspicion despite a good family history (n ¼ 147,42.2%), patient refusal (n ¼ 27, 7.8%) and no action or plandespite suspicion (n ¼ 16, 4.6%).

In this study, less than one-third (31.2%, 158/506) ofcancer patients of at least modest risk for HBOC werereferred by oncologists for genetic counselling. Inadequatefamily history evaluation and failure to recognise at-riskindividuals despite a good family history accounted foralmost 90% of non-referrals. These important physicianbarriers should and can potentially be rectified throughcontinued physician education, systematic screening bygenetic counsellors and clinic-based protocols.

S.G.W. Ow*, Y.F.L. Yong*, W.S. Chieng*, P.S. Phyu*, S.-C. Lee*y*Department of Hematology-Oncology,

National University Cancer Institute, SingaporeyCancer Science Institute,

National University of Singapore, Singapore

* Author for correspondence: S.-C. Lee, M.D,Department of Haematology-Oncology,

National University Cancer Institute,National University Health System, Singapore,

Level 7, Tower Block, 1E Kent Ridge Road,Singapore 119228. Tel: 65 67724621; Fax: 65 67775545.

E-mail address: csilsc@nus.edu.sg (S.-C. Lee).

References

[1] King MC, Wieand S, Hale K, et al. Tamoxifen and breast cancerincidence among women with inherited mutations in BRCA1and BRCA2: National Surgical Adjuvant Breast and BowelProject (NSABP-P1) Breast Cancer Prevention Trial. JAMA2001;286(18):2251e2256.

[2] Meijers-Heijboer H, van Geel B, van Putten WL, et al. Breastcancer after prophylactic bilateralmastectomy inwomenwith aBRCA1 or BRCA2 mutation. N Engl J Med 2001;345(3):159e164.

[3] Anderson B, McLosky J, Wasilevich E, Lyon-Callo S, Duquette D,Copeland G. Barriers and facilitators for utilization of geneticcounseling and risk assessment services inyoung female breastcancer survivors. J Cancer Epidemiol 2012;2012:1e11.

[4] Chieng WS, Lee SC. Discrepancy between initial high expres-sion of interest in clinical cancer genetic testing and actuallow uptake in an Asian population. Genet Test Mol Biomarkers2012;16(7):785e793.

[5] Chin TM, Tan SH, Lim SE, et al. Acceptance, motivators, andbarriers in attending breast cancer genetic counseling inAsians. Cancer Detect Prev 2005;29(5):412e418.

� 2013 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved

http://dx.doi.org/10.1016/j.clon.2013.11.029

Management of Oropharyngeal Cancer e UK Survey Shows Variationsin Practice

Sir d As recently reported by Oguejiofor and colleagues[1], p16, a surrogate marker for human papillomavirus(HPV), is the single most important prognostic variable fororopharyngeal cancer. Currently, >70% of oropharyngealcancers in Europe are HPV-positive [2], with excellentlong-term survival rates [3]. The treatment method does

not influence survival in non-randomised comparisons [4],but has a significant effect on long-term function [5,6],which is highly relevant in young patients with HPV-related disease.

Two distinct treatment modalities for oropharyngealcancer are established: primary chemoradiotherapy (CRT)