European Institute Of Oncology Research Articles

Central pathology laboratory review of HER2 and ER in early breast cancer: an ALTTO trial [BIG 2-06/NCCTG N063D (Alliance)] ring study

Choice of therapy for breast cancer relies on human epidermal growth factor receptor-2 (HER2) and estrogen receptor α (ER) status. Before randomization in the phase III Adjuvant Lapatinib and/or Trastuzumab Treatment Optimisation (ALTTO) trial for HER2-positive disease, HER2 and ER were centrally reviewed by Mayo Clinic (Rochester, MN, and Scottsdale, AZ) for North America and by the European Institute of Oncology (IEO; Milan, Italy) for the rest of world (except China). Discordance rates (local vs. central review) differed between Mayo and IEO. Among locally HER2-positive cases, 5.8 % (Mayo) and 14.5 % (IEO) were centrally HER2 negative. Among locally ER-positive cases, 16.2 % (Mayo) and 4.2 % (IEO) were centrally ER-negative. Among locally ER-negative cases, 3.4 % (Mayo) and 21.4 % (IEO) were centrally ER-positive. We, therefore, performed a ring study to identify features contributing to these differing discordance rates. Mayo and IEO exchanged slides for 25 HER2 and 35 ER locally/centrally discordant cases. Both laboratories performed IHC and FISH for HER2 using the HercepTest(®) and PathVysion HER2 DNA probe kit/HER2/centromere 17 probe mixture. IHC for ER was tested centrally using the monoclonal ER 1D5 antibody (Mayo) or the DAKO cocktail of ER 1D5 and 2.123 antibodies (IEO). Mayo and IEO confirmed the central HER2-negative result in 100 % of 25 cases. Mayo and IEO confirmed the central ER result in 29 (85 %) of 34 evaluable cases. The five Mayo-negative/IEO-positive cases were ER-positive when retested at Mayo using the DAKO ER cocktail. In this ring study, ALTTO ineligibility did not change when HER2 testing was performed by either IEO or Mayo central laboratories. However, a dual antibody ER assay had fewer false-negative test results than an assay with a single antibody, and there was more discordance between the two ER reagents than has been previously reported. Using even slightly different assay methods yielded different results, even between experienced central laboratories.

Nipple sparing mastectomy: does breast morphological factor related to necrotic complications?

Background:Nipple sparing mastectomy (NSM) can be performed for prophylactic mastectomy and the treatment of selected breast cancer with oncologic safety. The risk of skin and nipple necrosis is a frequent complication of NSM procedure, and it is usually related to surgical technique. However, the role of the breast morphology should be also investigated.Method:We prospectively performed an analysis of 124 NSM from September 2012 to January 2013 at the European Institute of Oncology, Milan, Italy, focusing on necrotic complications. We analyzed the association between the risks of skin necrosis and the breast morphology of the patients.Results:Among 124 NSM in 113 patients, NSM procedures were associated with necrosis in 22 mastectomies (17.7%) among which included partial necrosis of nipple-areolar complex (NAC) in 15 of 124 NSM (12.1%) and total necrosis in 4 cases (3.5%). The NAC was removed in 5 NSM cases (4%). The volume of breast removed was the only significant factor increasing the risk of skin necrosis. The degree of ptosis was not significantly related to the necrosis risk.Conclusions:Large glandular specimen increases the risk of NAC necrosis. The degree of ptosis and the distance between the sternal notch and the NAC have no significant impact on necrotic complications in NSM. To reduce the necrotic complications in large breast after NSM, reconstruction should better be performed with autologous flap or slow skin expansion using the expander technique.

No Link between Breast Cancer and Meningioma: Results from a Large Monoinstitutional Retrospective Analysis

The etiology of meningioma is largely unknown, although breast cancer has been suggested to play a role. A monoinstitutional, retrospective analysis was performed at European Institute of Oncology on 12,330 patients with breast cancer. The cumulative incidence of meningioma was estimated using the Kaplan-Meier method and the log-rank test was used to assess differences between groups. In total, 33 patients with meningioma were identified from a study population of 12,330, with a 10-year cumulative incidence of meningioma of 0.37%. We did not find a significantly increased risk of meningioma among patients with breast cancer or an association between the hormonal receptor status and the risk of meningioma (P = 0.65). Our results do not support a role of breast cancer or endocrine treatments in meningioma development. This analysis adds new information on a debated topic.

Abstract P3-09-06: Development and validation of a questionnaire for axillary web syndrome self-assessment

Abstract INTRODUCTION: Despite the great strides made in medical knowledge and technology, surgery still remains a necessary part of the breast cancer treatment protocol. Even with the employment of less aggressive techniques, surgical procedures still lead to post surgical sequelae and complications. The axillary web syndrome (AWS) is one such sequela which can lead to disability, reduced arm mobility and compromised quality of life. Currently, there is no diagnostic tool such as a self-validated questionnaire to detect AWS which may help the patient to seek the opportunity for immediate treatment. To improve diagnosis and patient education, the ST-AWS questionnaire was drafted and applied at the European Institute of Oncology (IEO). MATERIALS AND METHOD: We prospectively recruited patients from October 2012 to December 2012. Groups of patients who underwent ipsilateral sentinel lymph node biopsy and/or axillary dissection with or without plastic reconstruction procedures were registered. The complete physical examination by physiotherapist was set as a gold standard to evaluate the validity and reliability of ST-AWS. Axillary Web Syndrome general table AWS EVALUATION CATEGORIESYES 32 (%)NO 56 (%)p-value §AGE*< 5119 (59)24 (43)0.14 ≥ 5113 (41)32 (57) SCHOOLINGHigh28 (88)42 (75)0.16 Low4 (12)14 (25) BMI≤ 18,55 (16)0 (0)0.006 18,5 - 25,022 (68)32 (57) > 255 (16)24 (43) TIME OF SURGERY (min)*≤ 11912 (37)33 (59)0.05 > 11920 (63)23 (41) PLASTIC RECONSTRUCTIONYes25 (78)29 (52)0.02 No7 (22)27 (48) BREAST SURGERYMastectomy25 (78)34 (61)0.10 Quadrantectomy7 (22)22 (39) AXILLARY SURGERYAxillary Dissection20 (63)29 (52)0.33 Sentinel Lymph Node Biopsy12 (37)27 (48) N STAGE09 (28)25 (45)0.07 115 (47)16 (28) 22 (6)10 (18) 36 (19)5 (9) SENSIBILITY LOSSYes15 (47)9 (16)0.002 No17 (53)47 (84) * median values were used as cut off points § Chi-square, Fisher exact and Mantel-Haenszel Chi-Square tests RESULTS: 88 patients completed the questionnaire and the physical examinations and were included in the study. 32 patients had axillary web syndrome diagnosed, thus a 36% incidence. Median age was 51 years (range 22-78 years). The questionnaire achieved a sensitivity of 94%, a specificity of 91%, a positive prevalence value (PPV) of 86%, a negative prevalence value (NPV) of 96% and an accuracy of 92%. Comparing Gold Standard physical Evaluation and ST-AWS Questionnaire results PHYSICAL EVALUATION (GOLD STANDARD) NEGATIVEPOSITIVETOTALQUESTIONNAIRE NEGATIVE51253POSITIVE53035TOTAL563288Sensibility: 94%, Specificity: 91%, Accuracy:92%, PPV:86%, NPV:96% CONCLUSION: Our questionnaire achieves high sensitivity and predictive values, and we would recommend it as a screening-tool for auto-diagnosis of the axillary web syndrome. Nevertheless, the results of the ST-AWS should be confirmed by a physiotherapy examination. The main objective of the questionnaire is to enhance patient and therapist awareness of the problem, and prompt management in order to shorten the effects of this disability. Moreover, it may offer a tool to enhance body image acceptance after surgery. Further studies whereby the efficacy of the questionnaire is investigated in a larger, heterogeneous group and in different situations are warranted. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P3-09-06.

The Influence of Shc Proteins on Life Span in Mice

The signaling molecule p66Shc is often described as a longevity protein. This conclusion is based on a single life span study that used a small number of mice. The purpose of the present studies was to measure life span in a sufficient number of mice to determine if longevity is altered in mice with decreased Shc levels (ShcKO). Studies were completed at UC Davis and the European Institute of Oncology (EIO). At UC Davis, male C57BL/6J WT and ShcKO mice were fed 5% or 40% calorie-restricted (CR) diets. In the 5% CR group, there was no difference in survival curves between genotypes. There was also no difference between genotypes in prevalence of neoplasms or other measures of end-of-life pathology. At 40% calorie restriction group, 70th percentile survival was increased in ShcKO, while there were no differences between genotypes in median or subsequent life span measures. At EIO, there was no increase in life span in ShcKO male or female mice on C57BL/6J, 129Sv, or hybrid C57BL/6J-129Sv backgrounds. These studies indicate that p66Shc is not a longevity protein. However, additional studies are needed to determine the extent to which Shc proteins may influence the onset and severity of specific age-related diseases.

High Ki-67 score is indicative of a greater benefit from adjuvant chemotherapy when added to endocrine therapy in Luminal B HER2 negative and node-positive breast cancer

BackgroundThe indication of adjuvant chemotherapy for patients with highly proliferative estrogen receptor-positive breast cancer is controversial. We analyzed the predictive value of Ki67 for the efficacy of adjuvant chemotherapy in patients with estrogen receptor-positive, node-positive breast cancer. Patients and methodsWe identified 1241 patients with Luminal B early stage breast cancer with 1–3 axillary positive nodes who underwent surgery between 1995 and 2005 at the European Institute of Oncology and received adjuvant hormonotherapy and/or chemotherapy. Differences in the distribution of characteristics according to treatment were evaluated by the Chi-square test. To evaluate the effect of adding chemotherapy to hormonotherapy, the propensity score method was used to match patients' characteristics minimizing bias related to the non-random assignment of treatment. ResultsThe probability of receiving chemotherapy was significantly associated with age, tumor grade, degree of hormone responsiveness, tumor size and peripheral vascular invasion. The propensity score distribution was statistically different between the two treatment groups (p < 0.0001). The 5-year OS percentages were 95.8% (95% CI, 93.5–97.2) in the hormonotherapy group and 96.2% (95%CI, 94.4–97.4%) in the hormonotherapy/chemotherapy group (log-rank test p-value 0.663). The 5-year DFS percentages were 84.6% (95% CI, 81.0–87.6%) in the hormonotherapy group and 84.2% (95% CI, 81.3–86.7%) in the hormonotherapy/chemotherapy group (log-rank test p-value 0.388). However, when analyzing the 5-year DFS by Ki-67 distribution, Subpopulation Treatment Effect Pattern Plot (STEPP) analysis showed a beneficial effect of chemotherapy in patients with highly proliferative tumor (Ki-67 ≥ 32%). The interaction between Ki-67 and treatment was statistically significant (p = 0.027). ConclusionsKi67 expression identifies a subset of patients with Luminal B and node-positive breast cancer who could benefit from addition of adjuvant chemotherapy to hormonotherapy. Dichotomy was observed for Ki67 at 32% level.

Intraoperative radiotherapy versus external radiotherapy for early breast cancer (ELIOT): a randomised controlled equivalence trial

Intraoperative radiotherapy with electrons allows the substitution of conventional postoperative whole breast irradiation with one session of radiotherapy with the same equivalent dose during surgery. However, its ability to control for recurrence of local disease required confirmation in a randomised controlled trial. This study was done at the European Institute of Oncology (Milan, Italy). Women aged 48-75 years with early breast cancer, a maximum tumour diameter of up to 2·5 cm, and suitable for breast-conserving surgery were randomly assigned in a 1:1 ratio (using a random permuted block design, stratified for clinical tumour size [<1·0 cm vs 1·0-1·4 cm vs ≥1·5 cm]) to receive either whole-breast external radiotherapy or intraoperative radiotherapy with electrons. Study coordinators, clinicians, and patients were aware of the assignment. Patients in the intraoperative radiotherapy group received one dose of 21 Gy to the tumour bed during surgery. Those in the external radiotherapy group received 50 Gy in 25 fractions of 2 Gy, followed by a boost of 10 Gy in five fractions. This was an equivalence trial; the prespecified equivalence margin was local recurrence of 7·5% in the intraoperative radiotherapy group. The primary endpoint was occurrence of ipsilateral breast tumour recurrences (IBTR); overall survival was a secondary outcome. The main analysis was by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT01849133. 1305 patients were randomised (654 to external radiotherapy and 651 to intraoperative radiotherapy) between Nov 20, 2000, and Dec 27, 2007. After a medium follow-up of 5·8 years (IQR 4·1-7·7), 35 patients in the intraoperative radiotherapy group and four patients in the external radiotherapy group had had an IBTR (p<0·0001). The 5-year event rate for IBRT was 4·4% (95% CI 2·7-6·1) in the intraoperative radiotherapy group and 0·4% (0·0-1·0) in the external radiotherapy group (hazard ratio 9·3 [95% CI 3·3-26·3]). During the same period, 34 women allocated to intraoperative radiotherapy and 31 to external radiotherapy died (p=0·59). 5-year overall survival was 96·8% (95% CI 95·3-98·3) in the intraoperative radiotherapy group and 96·9% (95·5-98·3) in the external radiotherapy group. In patients with data available (n=464 for intraoperative radiotherapy; n=412 for external radiotherapy) we noted significantly fewer skin side-effects in women in the intraoperative radiotherapy group than in those in the external radiotherapy group (p=0·0002). Although the rate of IBTR in the intraoperative radiotherapy group was within the prespecified equivalence margin, the rate was significantly greater than with external radiotherapy, and overall survival did not differ between groups. Improved selection of patients could reduce the rate of IBTR with intraoperative radiotherapy with electrons. Italian Association for Cancer Research, Jacqueline Seroussi Memorial Foundation for Cancer Research, and Umberto Veronesi Foundation.

Trabectedin Plus Pegylated Liposomal Doxorubicin: The Return of a Treatment Option foR Ovarian Cancer

Future OncologyVol. 9, No. 12s ForewordFree AccessTrabectedin plus pegylated liposomal doxorubicin: the return of a treatment option for ovarian cancerJohn ClareJohn ClareLion's Den Communications Ltd, London, UK. Search for more papers by this authorEmail the corresponding author at john.clare@lionsdencommunications.comPublished Online:6 Nov 2013https://doi.org/10.2217/fon.13.203AboutSectionsPDF/EPUB ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareShare onFacebookTwitterLinkedInReddit Keywords: fully platinum-sensitiveovarian cancerpartially platinum-sensitivepegylated liposomal doxorubicintrabectedinManufacturing difficulties resulted in a shortage of pegylated liposomal doxorubicin (PLD), but these problems have recently been resolved and PLD is now available again. It follows that oncologists now have access to this important anticancer therapy and the combination of trabectedin (Yondelis®, PharmaMar, Madrid, Spain) plus PLD can once more be prescribed for the treatment of relapsed ovarian cancer, the topic under discussion at this symposium.Today we have a much greater understanding regarding which patients with ovarian cancer in particular will benefit the most from treatment with trabectedin plus PLD: ▪ The first group involves patients with partially platinum-sensitive disease;▪ The second group includes patients fully platinum-sensitive but who, for whatever reason, cannot be retreated with platinum therapy.These are important clinical problems that oncologists have to deal with in their daily practice and in this symposium we count on eminent experts in the field to present some of the most recent data on these topics under the chairmanship of Andres Poveda (Instituto Valenciano de Oncología, Valencia, Spain) and Eric Pujade-Lauraine (Hôpital Hôtel-Dieu, París, France). Key speakers at the symposium are Nicoletta Colombo (European Institute of Oncology, University of Milan, Bicocca, Milan, Italy), Maurizio D‘Incalci (IRCCS – Istituto di Ricerche Farmacologiche Mario Negri, Milan, Italy), Antonio González (MD Anderson Cancer Center, Madrid, Spain) and Isabel Ray-Coquard (Centre Léon Bérard, Lyon, France). To discuss the findings that are presented with the goal of providing an overall perspective we have the following experts: Jalid Sehouli (European Competence Center for Ovarian Cancer, Charité University Hospital, Berlin, Germany), Josep M del Campo (Vall d‘Hebron University Hospital, Barcelona, Spain) and Domenica Lorusso (Fondazione `IRCCS‘ National Cancer Institute, Milan, Italy).Financial & competing interests disclosureThe author has no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.Editorial assistance was provided by Content Ed Net, with funding from PharmaMar, Madrid, Spain.FiguresReferencesRelatedDetails Vol. 9, No. 12s eToC Sign up Follow us on social media for the latest updates Metrics History Published online 6 November 2013 Published in print December 2013 Information© Future Medicine LtdKeywordsfully platinum-sensitiveovarian cancerpartially platinum-sensitivepegylated liposomal doxorubicintrabectedinFinancial & competing interests disclosureThe author has no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.Editorial assistance was provided by Content Ed Net, with funding from PharmaMar, Madrid, Spain.PDF download

Platinum-Based Neoadjuvant Chemotherapy Followed by Radical Surgery for Cervical Carcinoma International Federation of Gynecology and Obstetrics Stage IB2-IIB

The objective of this study was to determine the response rate to chemotherapy, as well as the progression-free survival (PFS), the overall survival (OS), and the main prognostic factors in patients treated at the European Institute of Oncology in Milan, Italy. Retrospective data were collected on patients with uterine cervical carcinoma, International Federation of Gynecology and Obstetrics (FIGO) stage IB2 to IIB, who underwent platinum-based neoadjuvant chemotherapy (NACT) followed by radical hysterectomy. A total of 121 patients were studied. The median (range) age was 45 years old (23-69 years). The distribution of patients by International Federation of Gynecology and Obstetrics stage was as follows: n = 88 (73%) with stage IB2, n = 7 (6%) with stage IIA, and n = 26 (21%) with stage IIB. The median (range) tumor size was 50 mm (20-90 mm). Neoadjuvant chemotherapy involved a combination of cisplatin, paclitaxel, and ifosfamide in 80 patients (65%). Using this treatment, 112 patients (93%) received 3 cycles of NACT, whereas 6 (5%) received 4 cycles. Complete and partial pathology response was observed in 9 patients (7%) and 79 patients (66%), respectively. Adjuvant radiotherapy was not necessary in 65% of patients. A 5-year PFS and OS of 58% and 71%, respectively, were observed. Independent prognostic factors for PFS and OS were identified, including response to NACT, persistent lymph node metastases, and parametrial involvement. Neoadjuvant chemotherapy in this group of tumors is a promising treatment strategy and should be discussed with patients. Although these results are comparable to those obtained by standard chemoradiation treatment, one strategy should not be recommended over the other until the results of the ongoing phase 3 trial for NACT are released.

Survival Outcomes in Breast Cancer Patients With Low Estrogen/Progesterone Receptor Expression

IntroductionThe prognostic value of low estrogen and progesterone receptors expression (ER/PgR 1%-10%) in early breast cancer patients is still unclear. Patients and MethodsWe retrospectively analyzed 1424 consecutive patients with HER2/neu-negative and low endocrine receptors expression early breast cancer, submitted to surgery at the European Institute of Oncology between January 1995 and December 2009. Patients were classified according to the percentage of ER/PgR expression using immunohistochemistry. Group 1 with ER/PgR < 1%, and group 2 with ER/PgR 1% to 10%. ResultsGroup 1 (ER/PgR < 1%) included 1300 patients, and group 2 (ER/PgR 1%-10%) 124 patients. Median follow-up time was 74 months (range, 3-192 months). The 5-year disease-free survival (DFS) rate was 74% (95% confidence interval [CI], 72%-77%) for group 1, and 79% (95% CI, 70%-86%) for group 2 (P = .16). The 5-year overall survival (OS) rate was 86% (95% CI, 84%-88%) in group 1 and 90% (95% CI, 83%-95%) in group 2 (P = .13). In patients without lymph node involvement, the 5-year OS rate was 92% (95% CI, 89.5%-93.6%) for group 1 and 98% (95% CI, 90.2%-99.8%) for group 2 (P = .061). One hundred ten patients received endocrine therapy with no significant effect on DFS (P = .36) and OS (P = .30). ConclusionThe ER/PgR 1%-10% group had a slight, but not statistically significant, better prognosis than the ER/PgR <1% group. Further studies are needed to identify the appropriate clinical approach in this subset of patients with low ER/PgR expression (ER/PgR 1%-10%), HER2-negative early breast cancer.

Newly diagnosed and relapsed epithelial ovarian carcinoma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up

Newly diagnosed and relapsed epithelial ovarian carcinoma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up N. Colombo, M. Peiretti, G. Parma, M. Lapresa, R. Mancari, S. Carinelli, C. Sessa & M. Castiglione On behalf of the ESMO Guidelines Working Group* Division of Gynecologic Oncology; Division of Pathology, European Institute of Oncology, Milan, Italy; Oncology Institute of Southern Switzerland, Bellinzona, Switzerland; Montabone Unit for New Drug Development, Fondazione IRCCS, Istituto dei Tumori di Milano, Milan, Italy; RGT, University of Geneva, Geneva, Switzerland

Pathological features and survival outcomes of very young patients with early breast cancer: How much is “very young”?

We collected information on 497 consecutive breast cancer patients aged less than 35 years operated at the European Institute of Oncology. The main aim of the study is to compare biological and clinical features dividing the population by age: <25 years, 25–29 and 30–34 years old. Pattern of recurrence and survival were also analyzed.Patients aged <25 years had 81.8% poorly differentiated tumors compared with 66.7% and 56.5% in the 25–29 and 30-34 groups, respectively; no other significant difference were found in the distribution of clinical and immunohistochemical features The distribution of Luminal A and B, Triple Negative and HER2 subtypes (immunohistochemically defined) was not statistically different among the three age groups. No difference was found in the incidence of loco-regional relapses, distant metastases, disease-free survival (p = 0.79) and overall survival (p = 0.99) between the three age groups. This latter findings was confirmed using age as a continuous variable assuming a linear association between age and the outcomes considered, too.In conclusion, our data indicate that the group of patients with breast cancer below 35 years is essentially a homogenous group when classical clinical and immunohistochemical features were considered.

Outcomes of Patients With Breast Cancer Who Present With Ipsilateral Supraclavicular or Internal Mammary Lymph Node Metastases

BackgroundThe prognostic implications of internal mammary (IM) and supraclavicular (SC) node involvement in locally advanced breast cancer is still unclear. Patients and MethodsWe evaluated 107 patients with IM (n = 65) or SC (n = 42) node involvement who underwent operation at the European Institute of Oncology between 1997 and 2009 to assess their prognostic features. We subsequently analyzed matched cohorts, using the 107 patients as cases and another group of patients as a control cohort, to evaluate prognostic differences between patients with and those without IM or SC node involvement. ResultsFive-year disease-free survival (DFS) was 84% in IM vs. 38.8% in SC node involvement (P < .0001), and 5-year overall survival (OS) was 96.9% in IM node vs. 57.1% in SC node involvement (P < .0001). No difference in outcome was found between patients with and controls without IM node involvement. Conversely, a statistically significant difference in DFS and locoregional recurrence was observed in patients with SC node involvement compared with controls without SC node involvement. ConclusionSC node involvement correlated with a significantly poorer outcome in patients with locally advanced breast cancer. Adequate staging, including biopsy of suspicious locoregional ipsilateral lymph nodes, is mandatory in these patients. Patients with IM or SC node involvement should be treated with curative intent using combined-modality treatments.

Immediate breast reconstruction with expander in pregnant breast cancer patients

BackgroundBreast reconstruction after mastectomy is currently considered an essential component in managing breast cancer patients, particularly those diagnosed at a young age. However, no studies have been published on the feasibility of immediate breast reconstruction in patients diagnosed and operated during the course of gestation. MethodWe retrospectively identified all breast cancer patients who were subjected to mastectomy and immediate breast reconstruction during pregnancy at the European Institute of Oncology between 2002 and 2012. Patient demographics, gestational age at surgery, tumor stage, adjuvant treatment, details of the surgical procedures, surgical outcomes and fetal outcomes were analyzed. ResultsA total of 78 patients with breast cancer diagnosed during pregnancy were subjected to a surgical procedure during the course of gestation. Twenty-two patients had mastectomy; of whom 13 were subjected to immediate breast reconstruction. Twelve out of 13 patients had a two-stage procedure with tissue expander insertion. Median gestational age at surgery was 16 weeks. No major surgical complications were encountered. Only one patient elected to have an abortion, otherwise, no spontaneous abortions or pregnancy complications were reported. Median gestational age at delivery was 35 weeks (range: 32–40 weeks). No major congenital malformations were reported. At a median follow-up of 32 months, all patients are alive with no long-term surgical complications. ConclusionsThis is the first study of immediate breast reconstruction in pregnant breast cancer patients. Tissue expander insertion appears to ensure a short operative time, and does not seem to be associated with considerable morbidity to the patient or the fetus. Hence, it could be considered in the multidisciplinary management of women diagnosed with breast cancer during pregnancy.

Reply to M.L. Friedlander et al

In a recent letter, Friedlander et al discuss the role of symptom benefit in platinum-resistant or -refractory ovarian cancer. Qualityof-life (QoL) assessments are of extreme importance in this patient population and particularly in this setting of platinum-resistant, recurrent ovarian cancer. For this reason, evaluation of patient-reported symptoms and QoL by the Functional Assessment of Cancer TherapyOvary (FACT-O) and FACT-O Symptom Index were secondary objectives in the phase III study that compared patupilone with pegylated liposomal doxorubicin in this patient population, and the results were published online as supplementary material. As reported, these scores trended lower (suggesting a decrease in the QoL) in the patients in the patupilone arm compared with those in the pegylated liposomal doxorubicin arm. This result is intriguing in that patupilone produced a higher overall response rate compared with pegylated liposomal doxorubicin (15.5% v 7.9%). Thus, although one might expect a possible positive impact on disease-related symptoms, the converse was observed. This may be reflective of the relatively low response rate, which did not translate into an appreciable impact on QoL. Alternatively, the QoL may have been negatively affected by chemotherapyrelated symptoms, which may reflect the unique toxicity profile for patupilone compared with pegylated liposomal doxorubicin. A more in-depth assessment would be required to derive a more definitive conclusion, but as future trials measure and report QoL and symptom benefit assessments, these types of comparative analyses will become increasingly common. Nicoletta Colombo University of Milan-Bicocca and European Institute of Oncology, Milan, Italy

PET/CT and breast cancer subtypes

Breast cancer is a profoundly heterogeneous disease that includes a number of distinct entities with specific pathological features, biological behaviours and different sensitivities to systemic and targeted therapies [1–4]. The recent development of high-throughput molecular methods offers new opportunities to capture the wide range of this variability. Indeed, the novel molecular techniques of gene expression profiling permit evaluation of the expression of thousands of genes in a large number of tumours, so that a fully comprehensive portrait or profile of the different molecular pathways can be obtained. The reproducibility and the clinical usefulness of assays based on gene expression have been demonstrated with increasing confidence over the past decade, but cost considerations limit the wide availability of these techniques [5]. Immunohistochemical (IHC) determination of oestrogen and progesterone receptors (ER and PgR), the detection of overexpression and/or amplification of human epidermal growth factor receptor 2 (HER2) and the Ki67 labelling index have been defined as a convenient alternative to molecular subtyping and are considered a sufficient to guide therapeutic choices [6]. Several studies have investigated the correlation between these clinical/pathological prognostic and predictive markers and the levels of radiotracer uptake by primary breast tumours, measured as maximum standardized uptake value (SUVmax), during F-FDG PET/CT. High SUVmax was found to be significantly correlated with ER negativity, PgR negativity, triple negativity and Ki67 values, while conflicting results were found for the relationship with HER2 status [7–12]. In the present issue of the European Journal of Nuclear Medicine and Molecular Imaging, Garcia Vicente et al. take a step forward in this approach to evaluation. They analysed the correlation between the glycolytic characteristics of primary breast tumours and their molecular subtypes. The authors prospectively evaluated 168 patients who were submitted to FDG PET/CT before neoadjuvant therapy for locally advanced breast cancer. Tumour subtypes were classified by IHC surrogates as luminal A, luminal B-HER2(−), luminal B-HER2(+), HER2(+) or basal (triple negative), following the recommendations of the 12th St Gallen International Breast Cancer Conference. Statistically significant differences were found in semiquantitative metabolic parameters among the different subtypes, with greater values in HER2(+) and basal tumours [13]. These results are not unexpected, as the relationship between increased glucose metabolism and tumour aggressiveness is well known. This is one of the first studies demonstrating a correlation between molecular and glycolytic phenotypes of breast cancer. Humbert et al. found that baseline FDG uptake of primary tumours and its early response to neoadjuvant chemotherapy may vary according to the IHC subtype of the breast cancer. Triple-negative tumours showed the highest baseline SUV. After the first course of therapy the decrease in SUV was significantly higher in triple-negative and HER2-positive subtypes. Pathological complete response (pCR) occurred more often in these two subtypes, rather than in luminal tumours, and the relative change in SUV was predictive of pCR only in HER2-positive tumours with an accuracy of 76 % [14]. Zhang et al. evaluated 244 patients with metastatic breast cancer. They found that molecular subtype, visceral metastases and number of organs bearing metastases could be used to predict logarithmic values of SUVmax only in previously untreated metastatic breast cancer [15]. L. Gilardi :G. Paganelli (*) Division of Nuclear Medicine, European Institute of Oncology, via Ripamonti 435, 20141 Milan, Italy e-mail: divisione.medicinanucleare@ieo.it

Prognostic effect of beta blockers (BB) in triple-negative breast cancer (TNBC) patients.

1061 Background: BB drugs have been used for decades worldwide, typically to treat hypertension and arrhythmias. Despite its therapeutic indication, evidence from recent epidemiological studies suggested that BB intake can improve prognosis of patients (pts) with cancer. With the present study we aimed at assessing whether BB intake is associated with improved prognosis in postmenopausal pts with TNBC, which represents one of the most aggressive cancers. Methods: We retrospectively identified 659 postmenopausal pts operated between 1997 and 2008 at the European Institute of Oncology, Milan, for a primary TNBC. Pts with advanced disease at diagnosis, presurgical systemic treatment or history of other cancers were excluded. The effect of BB intake on the risk of breast cancer recurrence and death from breast cancer (BC) was evaluated through competing risk survival analyses and multivariable Cox regression models. Results: At the time of cancer diagnosis, 61 pts (9.3%) out of 659 were currently using BB, while 598 (90.7%) were not. Median age was 63 years for the BB users and 60 years for the non-users (p value 0.048). All other characteristics—such as tumor size, lymph-nodal involvement, Ki-67, tumor grade, perivascular invasion, type of surgery and adjuvant therapy—were equally distributed between BB users and non-users. Median follow-up was 6 years for both groups. The 5-year cumulative incidence of BC recurrences was 11.7% and 24.1% for BB users and non-users, respectively (p = 0.030). After adjusting for age, tumor size, lymph nodal involvement, grade, perivascular invasion and use of other antihypertensive drugs, the beneficial impact of BB use remained statistically significant, with an hazard ratio of 0.44 (95% CI 0.21-0.98; p = 0.044). The 5-year cumulative incidence of BC deaths was 8.2% and 12.5% for BB users and non-users, respectively (p = 0.185). Hypertension and antihypertensive drugs other than BB did not have any significant impact on recurrence and survival. Conclusions: In this series of postmenopausal pts with primary TNBC, BB intake was associated with a significantly decreased risk of BC recurrence. Additional studies evaluating the potential benefits of BB on cancer prognosis are warranted.

Management of breast cancer during pregnancy: Results of a large registry from a single institution.

589 Background: Given the rising trend of delaying pregnancy to later in life, more women are diagnosed with breast cancer during pregnancy. Management is still controversial and relies on expert guidelines. Thus the experience of single centres with high patients’ volume remains of interest. Methods: All breast cancer patients (pts) diagnosed at the European Institute of Oncology (IEO) in Milan were included in a specific registry since 1995. Results: Out of 8340 patients &lt; 47 y/o registered up to Dec 2012, 167 were diagnosed during pregnancy (2%). Median age was 36 years (24-47y). Median gestational age was 18 weeks (1-38 w). 73 % pts had a pT1-2 tumor, with positive nodes in 48%. 9,6% had luminal A, 38% luminal B, 26% basal like and 16% HER2+ tumors, according to St Gallen criteria. 29/167 pts (17%) opted for an induced abortion. Of the remaining 97 pts, 81 (84%) underwent definitive surgery during pregnancy; 58 (72%) and 23 pts (28%) had quadrantectomy and mastectomy, respectively. Immediate breast reconstruction was performed in 13 cases. Sentinel node procedure (SLN) was performed in 42 pts (52%), with positive axilla in 10 pts. 41 pts (51%) received chemotherapy during pregnancy. Regimens included weekly epirubicin (24 pts), EC/AC (12 pts), FAC/FEC (3 pts), q21 epirubicin (2 pts). No G3-G4 toxicities were reported. No pregnancy complications were observed, with the exception of 1 case of premature delivery at 28 weeks. Median gestational age at delivery was 36 weeks (29-40 w). No major malformations were observed. Gestational age at birth and birth-weight were similar in babies who received chemotherapy in-utero (36 w and 2555g) and in babies who did not receive gestational chemotherapy (37w and 2600g). At a median follow-up of 42 months (range: 1-178 m), all children had normal neurological and physical development with no late adverse effects observed. Conclusions: Managing breast cancer during pregnancy should follow standard practice as in non-pregnant pts. Surgeries like SLN and breast reconstruction were performed with no serious complications. Our results further emphasize the safety of anthracycline-based gestational chemotherapy without major effects on pregnancy course or fetal health.

Second primary tumors in cancer patients: A retrospective analysis based on institutional tumor registry.

1595 Background: The relative risk of developing a second tumor by site of primary tumor or gender is still unclear. Methods: We retrospectively analyzed data of 24,224 consecutive patients admitted to the European Institute of Oncology between 2000 and 2006 for a first primary invasive tumor. All the data were extracted from the institutional Tumor Registry. All tumors were registered and indexed within the same patient’s record. We limited the analysis to the patients who were diagnosed and received at least one treatment in IEO for their first primary tumor. Follow-up was based on the last registered patient’s control visit. Cumulative incidence was compared across different subgroups by means of the Gray test. The observed cases of second metachronous primary tumors was compared with the number of cancers we expected from the general Italian population. We used the standardized incidence ratio (SIR), defined as the ratio of the number of second cancers observed to the number of second cancers expected, to estimate the relative risk of second cancers, and we calculated 95% confidence intervals (95% CIs) by applying the Wilson and Hilferty approximation for chi-square percentiles. Results: In this population the 5-year cumulative incidence of a second tumor on the average population was 5.0%, SIR (CI 95%) was 1.3 (1.2-1.4). The Table reports details on observed versus expected second metachronous primary tumors by first tumor site. Conclusions: Cancer patients have a higher risk of a second primary tumor than general population. [Table: see text]

Popcorn Effect

To the Editor: In the late 1970s, neodymium yttrium-aluminium-garnet (Nd-YAG) laser photoradiation was used bronchoscopically by a group of French physicians to achieve recanalization of the bronchial lumen obstructed by exophytic tumors.1 Thirty years later, bronchoscopic YAG laser therapy still has an important role in the palliation of patients with inoperable lung cancer; particularly those requiring immediate relief of bronchial obstruction.2 Although fire in the airway is a well-recognized hazard of the use of the CO2 laser, only anecdotal reports have been described related to intratracheal combustion during Nd-YAG laser treatment of the endobronchial lesions.3 By adhering to safety principles for Nd-YAG laser applications in the endobronchial tree, airway fires or explosion can be effectively prevented or adequately controlled to achieve radical tumor resection without any significant risk.4 We report a case of isolated main carina metastasis from non–small cell lung cancer treated by rigid bronchoscopy (Fig. 1).FIGURE 1: Bronchoscopic view of the tumor before starting laser resection.Controlled Nd-YAG laser energy using long, low-power, single-pulse mode was delivered for coagulation. Suddenly the left half of the lesion exploded with a loud noise scattering the burnt tissue all over the tracheobronchial tree. Incidentally there was no damage to the surrounding structures (Fig. 2). At the end of the procedure the whole lesion was completely resected (Fig. 3). We continued with the procedure until the entire endobronchial portion of the lesion was ablated.FIGURE 2: Bronchoscopic view of tumor explosion caught in the act.FIGURE 3: Bronchoscopic view at the end of the procedure, disclosing complete tumor resection.The reported phenomenon is referred to as “popcorn effect.” Obviously it is difficult to document it in pictures. The degree of tissue effects caused by the laser is due to the combination of absorption, scatter, transmission, and reflection of the light (photon) within the tissue. At temperatures above 65°C, protein denaturation and surface blanching takes place. Tissue desiccates and shrinks at temperatures above 90 to 100°C; and over 100°C, carbonization of the tissue takes place. Blackening of the tissue leads to the focused absorption of the laser energy and eventual vaporization of the tissue. In addition, concomitant vaporization of the intracellular and interstitial water can cause rapid rise in its volume within the tissue, which eventually leads to noisy expulsion of the vapor (popcorn effect).5 This explosion is unrelated to the amount of FiO2 being delivered. The purpose of reporting this event is that popcorn effect is relatively benign and the bronchoscopist can continue to work through the event. This effect can be avoided by avoiding carbonization of the tissue and applying laser energy diffusely over the lesion. In conclusion, Nd-YAG laser tumor resection is a safe procedure. Side effects such as a “popcorn” explosion are intriguing, but in the experienced hands it can be effectively managed without any injury to the patient. Francesco Petrella, MD* Sergio Cavaliere, MD* Lorenzo Spaggiari, MD, PhD*,† *Division of Thoracic Surgery, European Institute of Oncology †University of Milan School of Medicine, Milan, Italy