Surgical procedure for breast cancer is not without its side effects and one such side effect is axillary web syndrome (AWS), characterized by palpable fibrotic-like cords in the operated arm. As physical evaluation is the only gold standard method used, our study aims to assess the incidence and early detection of AWS with a self-assessment questionnaire.

BACKGROUND To assess the prognostic role of human epidermal growth factor receptor 2 (HER2) overexpression in patients with ductal carcinoma in situ (DCIS). PATIENTS AND METHODS We identified patients with HER2-positive DCIS among a population of 1667 cases, prospectively diagnosed and surgically treated at the European Institute of Oncology from 1996 to 2008. Rates of subsequent DCIS or invasive cancer in HER2-positive disease were estimated. We evaluated Cumulative Incidence of In Situ Breast Cancer Recurrence (isBCR), INvasive Breast Cancer Recurrence (IBCR) and any Breast Cancer Recurrence (BCR). isBCR, IBCR and BCR were defined as the time from surgery to breast cancer recurrence as first event (in situ, invasive or both, respectively) or last visit in case of no events. RESULTS We identified 560 (33.5%) patients with HER2-positive DCIS. The median follow-up was 7.6 years (interquartile range 5.9-9.5). We observed 422 events out of 1667 patients, with 141 in situ recurrences, 201 invasive recurrences and 80 other events (64 second primaries and 16 deaths). The 10-year isBCR proportions were 11.8% [95% confidence interval (CI) 9.0% to 15.4%] in the HER2-positive group and 8.8% (95% CI 6.9% to 11.0%) in the HER2-negative group (Gray test, P = 0.010). At multivariable analysis, the adjusted risk of isBCR was higher in the HER2-positive group than in the HER2-negative group [hazard ratio (HR) HER2 positive versus negative: 1.59 (95% CI 1.06-2.39)]. We observed significant differences both in BCR and isBCR for patients treated by quadrantectomy without radiotherapy versus patients treated with radiotherapy [adjusted HR HER2 positive versus negative: 1.53 (95% CI 1.07-2.18) and adjusted HR HER2 positive versus negative: 2.18 (95% CI 2.18-3.69), respectively]. CONCLUSION HER2 overexpression predicts an increased risk of isBCR. Radiotherapy reduces local failure rates in HER2-positive DCIS.

Purpose This retrospective study aimed to determine the feasibility, accuracy, and recurrence rates of lymphoscintigraphy and the new sentinel lymph node biopsy (SLNB) for patients with ipsilateral breast tumor recurrences who were treated previously with conservative surgery and had negative SLNB results. Methods The study was conducted at the European Institute of Oncology in Milan and included 212 patients with the diagnosis of operable local breast cancer recurrence. They had been treated previously with conservative surgery and showed negative SLNB results. They subsequently underwent additional breast surgery and a second SLNB between May 2001 and December 2011. Results Preoperative lymphoscintigraphy demonstrated at least one new axillary sentinel lymph node (SLN) in 207 patients (97.7 %), whereas no drainage was observed in five patients (2.3 %). One or more SLNs were surgically removed from 196 of the 207 patients. Isolation of SLNs from the remaining 11 patients could not be accomplished. The success rate for the SLNB was 92.5 %. Extra-axillary drainage pathways were visualized in 17 patients (8 %). The annual axillary recurrence rate after a median follow-up period of 48 months was 0.8 %, and the cumulative incidence of axillary recurrence at 5 years was 3.9 %. Conclusions A second SLNB should be considered for patients with operable local breast tumor recurrence who underwent conservative surgery and had negative SLNB results. The procedure is technically feasible and accurate for selected patients.

Aim: It is established that axillary dissection (AD) can be safely avoided in breast cancer patients with a negative sentinel node (SN). In the present study we assessed whether the rate of axillary disease was sufficiently low on long term follow-up to consolidate the policy of AD avoidance.Methods: We retrospectively analysed data on 5262 consecutive primary breast cancer patients with clinically negative axilla and negative SN, treated from 1996 to 2006, who did not receive AD. We used univariate and multivariate analyses to assess the influence of patient and tumour characteristics on first events and survival. The primary endpoint was the development of axillary disease as first event.Results: After a median follow-up of 7.0 years (interquartile range 5.4-8.9 years) survival for the series was high (91.3%; 95% CI 90.3-92.3 at 10 years) and only 91(1.7%) patients developed axillary disease as first event. Axillary disease was significantly more frequent in patients with the following characteristics: <35 years at diagnosis, tumour >1 cm, multifocality/multicentricity, G3, ductal histotype, Ki67 >= 30%, peritumoral vascular invasion, luminal B-like subtype, HER2 positivity, mastectomy, and not receiving radiotherapy.Conclusion: Long-term follow-up of our large series confirms that axillary metastasis is infrequent when AD is omitted in SN-negative breast cancer patients, and has low impact on overall survival. (C) 2014 Elsevier Ltd. All rights reserved.

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.

Abstract Background: Neoadjuvant endocrine therapy demonstrated activity in endocrine responsive locally advanced breast cancer. Proper duration of neoadjuvant therapy has not yet established. We aimed to assess the efficacy and safety of longer duration of letrozole alone or combined with triptorelin in pre-or postmenopausal breast cancer patients. Methods: Premenopausal and postmenopausal patients (pts) with ER and PgR-positive > 50% of the cells, HER2-negative, T2-T4b breast cancer were considered eligible. Patients received letrozole 2,5 mg per day (plus triptorelin 3,75 mg/month in premenopausal pts) for 3-9 months. Tumor response was measured by caliper, ultrasound (US) and mammography. The primary endpoint was overall tumour response (ORR) (complete response plus partial response), during the neoadjuvant treatment period for the intention-to-treat population. Results: Between 2009 and 2013, 54 pts were enrolled and 46 (34 pre- and 12 post-menopausal) pts were evaluable for ORR. Median age was 44 and 55 years, respectively. 44 patients are evaluable. The ORR was 77% in the premenopausal group and 67% in the postmenopausal group. One premenopausal patient had a pathological complete response (pCR). The mean time to complete/partial response was 4.9 months (95% CI: 3.8-6.0) in the premenopausal group and 3.6 months (95% CI: 0.8-6.4) in the postmenopausal group. Overall, 56% of premenopausal and 58% of postmenopausal pts underwent breast conservative surgery. Ki67-LI after surgery had a mean decrease of 33% (95% CI: 16%-50%, p-value = 0.0005) and 42% (95% CI: 18%-65%, p-value = 0.0030) in pre-and postmenopausal pts, respectively. Therapy was well tolerated in both groups with no grade 3/4 toxicity. The most common adverse events in both groups were hot flashes, fatigue, arthralgias/stiffness, and myalgias. Conclusions: The results of this preliminary analysis support neoadjuvant endocrine therapy for a duration of up to 9 months. The combination of letrozole plus triptorelin might represent an alternative neoadjuvant treatment option for premenopausal women with early stage endocrine-responsive breast cancer. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P1-15-03.

The aim of this analysis was to investigate the usefulness of Ki-67 labeling index (LI) for the identification of different prognostic subgroups in primary node-negative, triple negative breast cancer (TNBC) patients. From January 1997 to December 2005, 1,053 patients operated for TNBC were identified through the institutional clinical database. The study was performed in accordance with REMARK criteria. The relationship between Ki-67LI and the risk of breast-related deaths was evaluated with a multivariable Cox regression model. Cubic splines were used to model Ki-67LI as a continuous variable. We selected 496 consecutive patients with node-negative TNBC. Median age was 52 years, median Ki-67LI 48 % (range 4–95), and median follow up 6 years (range 0.5–13). Total deaths and deaths from BC were 52 (10.5 %) and 38 (7.7 %), respectively. Ki-67LI increased with decreasing age ( P < 0.01), increasing tumor size ( P < 0.01), and grade ( P < 0.01). When analyzing Ki-67LI as a continuous variable, the risk of death from BC increased steeply with increasing Ki-67LI up to about 35 % and remained flat for higher values (adjusted effect of Ki-67 P = 0.049; adjusted nonlinear effect P = 0.021). Accordingly, when dividing patients into lower (≤35 %) and higher (>35 %) Ki-67LI subgroups, the 5-year cumulative incidence of breast-related deaths were 2.3 and 9.0 %, respectively, with an adjusted HR >35 vs ≤35 of 2.3 (95 % CI 1.0–5.8, P = 0.046). Within the group of patients with node-negative TNBC, Ki-67LI was associated with different prognoses subgroups. Ki-67LI might be useful in the design of trials of risk-adapted adjuvant therapies.

BACKGROUND The immunohistochemical (IHC) evaluation of estrogen receptor (ER), progesterone receptor (PgR), Ki-67 and HER2 is considered a surrogate means for identifying the molecular subtypes of breast cancer with different prognosis. PATIENTS AND METHODS We explored patterns of recurrence in 4837 women with breast cancer defined as Luminal B (ER-positive and/or PgR-positive, HER2 positive and/or Ki-67≥14%) by IHC classification. We evaluated four subgroups within the Luminal B subtype according to HER2 expression and PgR status. RESULTS Patients within the ER+/PgR+/HER2- subgroup presented a 5-year breast cancer-related survival (BCS) of 97% (95% confidence interval (CI), 96-97) and overall survival (OS) of 95% [95% CI, 95-96], the best survivals of the Luminal B subgroups. In the multivariate analysis, the ER+/PgR-/HER2- subgroup was associated with a reduced BCS (HR 1.71; 95%CI, 1.25-2.35) and OS (HR 1.47; 95%CI, 1.10-1.96) when compared with the ER+/PgR+/HER2- subgroup. Also patients within the ER+/PgR-/HER2+ subgroup had a reduced BCS (HR 1.93; 95%CI, 1.32-2.83) and OS (HR 1.62; 95%CI, 1.14-2.30) when compared with ER+/PgR+/HER2- subgroup. On the other hand, no statistically significant differences were found with regard to BCS and OS among patients with ER+/PgR+/HER2+ and patients with ER+/PgR+/HER2- disease. CONCLUSIONS PgR loss identifies Luminal B breast cancer subgroups at higher risk of relapse and death, both with HER-2-positive and HER-2-negative disease.

BACKGROUND:The identification of special types of breast cancer might be of value in assessing prognosis and predicting response to therapy.METHODS:A total of 7372 consecutive patients with immunohistochemically defined luminal invasive breast cancer operated at the European Institute of Oncology between 1997 and 2005 were included. We then explored patterns of recurrence by histological type. Median follow-up was 5.8 years.RESULTS:Tumors from 5707 patients were classified as invasive ductal cancer (IDC) not otherwise specified (NOS), 851 lobular, 338 mixed ductal and lobular, 250 cribriform, 143 mucinous and 83 tubular carcinomas. Compared with IDC NOS disease-free survival (DFS) was significantly longer in patients with cribriform tumors [5-year DFS 97.9% versus 87.4%; hazard ratio (HR) = 0.48; P = 0.015) and in pooled cribriform plus tubular carcinomas (5-year DFS 98.7% versus 87.4%; HR = 0.45; P = 0.005). Mucinous tumors presented similar DFS if compared with IDC (5-year DFS 93 % versus 87.4%; HR = 1.03; P = 0.91). Conversely, DFS was poorer for patients with lobular carcinoma (5-year DFS 86.8% versus 87.4%; HR = 1.27; P = 0.01).CONCLUSIONS:The diagnosis of tubular, cribriform and lobular carcinomas carry distinct prognostic implications. The identification of these special types has a significant utility in luminal breast cancer and should be considered in therapeutic algorithms.

To assess the prognostic value of presurgical CA15.3 in a large cohort of patients with early breast cancer. A total of 7.942 consecutive patients with breast cancer operated at the European Institute of Oncology between 1998 and 2005 and with presurgical values of CA 15.3 available were included. We explored patterns of recurrence by baseline CA 15.3 values. Mean CA15.3 was 17.0 U/ml. CA15.3 was associated with age, tumor size, nodal involvement, Ki-67 labeling index, grade, HER2 expression, molecular subtype, and perivascular invasion. CA15.3 was independently associated with distant metastases [HR > 20 U/ml vs. ≤ 20 U/ml: 1.34 (95% CI 1.15–1.56)] and death [HR > 20 U/ml vs. ≤ 20 U/ml: 1.30 (95% CI 1.11–1.53)]. When considering CA15.3 as continuous variable, we observed a constant risk of metastasis and death from the lowest values to about 15–20 U/ml, and then a significantly increasing risk with increasing values of CA15.3. Finally, CA15.3 provided significant additional information to the common prognostic factors to predict the occurrence of metastases (C-index P value 0.04). In patients with operable breast cancer, presurgical CA15.3 value is an independent prognostic factor for metastases and deaths. CA15.3 provides additional information to the common prognostic factors and should be considered in the adjuvant therapeutic algorithm.

Knowledge is limited about prognostic significance of breast cancer subtypes among women with small invasive node-negative breast tumours. We explored patterns of recurrence in 1691 women with pT1mic/T1a/T1b, pN0 and M0 breast cancer according to four immunohistochemically defined tumour subtypes: (i) Luminal A (ER-positive, PgR-positive, HER2-negative and Ki-67 < 14%); (ii) Luminal B (ER-positive and/or PgR-positive, HER2-positive and/or Ki-67 ≥ 14%); (iii) HER2-positive, both endocrine receptors absent; and (iv) Triple Negative. At multivariate analysis, women with the Triple Negative breast cancer subtype had an increased risk of loco-regional relapse (LRR) (Hazards Ratio (HR) 3.58; 95%CI: 1.40–9.13) and breast cancer related events (HR 2.18; 95%CI: 1.04–4.57). Overall, Luminal B subtype was not associated with a statistically significant increased risk of recurrence compared with Luminal A, while patients with Luminal B subtype tumours overexpressing HER2 had a 2 fold risk of reduced breast cancer related survival (BCS), but not an increased risk of LRR and distant metastases. Women with HER2 breast cancer subtype had a statistically significant increased risk of LRR (HR 4.53; 95%CI: 1.56–13.1), distant metastases and reduced BCS (HR 3.22; 95%CI: 1.44–7.18) and overall survival (HR 2.87; 95%CI: 1.05–7.89) when compared with the Luminal A subtype, at multivariate analysis. In conclusion, women with small size, node-negative, breast cancer are at higher risk of relapse if with HER2-positive endocrine receptor absent or Triple Negative disease.

BACKGROUND:As few data are available on irradiation of the draining nodes after conservative surgery (CS), this study was designed to identify patients with T1-T2 breast cancer and one to three positive axillary nodes who needed regional radiotherapy (RT).PATIENTS AND METHODS:Five hundred seventy-five patients were treated between 1988 and 2001 with CS and RT to the breast. All but three received adjuvant chemotherapy and/or hormone therapy. Risk factors for and the relationships between local, nodal and distant relapses were analyzed.RESULTS:At a median follow-up of 7.3 years, the 10-year probability of survival free of local relapse, nodal relapse and distant metastases were 92.8%, 94.0% and 84.9%, respectively. Independent predictors of local relapse were the positive/excised node ratio, margin status and age. Predictors of nodal relapse were tumor grade, hormone receptor and margin status. Significant risk factors for distant metastases were tumor stage, grade, hormone receptor and margin status. Local and nodal relapses were related significantly with distant metastases. Only local and distant relapses were linked by temporal sequence (P=0.03).CONCLUSIONS:Overall relapse rates were low in these patients and different mechanisms appeared to underlie local, nodal or distant relapse.

BACKGROUND There is limited knowledge about prognosis of selected breast cancer subtypes among very young women. PATIENTS AND METHODS We explored patterns of recurrence by age according to four immunohistochemically defined tumor subtypes: Luminal A and Luminal B (estrogen receptor positive and/or progesterone receptor positive and either human epidermal growth factor receptor 2 (HER2) positive and/or high Ki-67), HER2-positive (and) endocrine receptor absent and Triple Negative, in 2970 premenopausal patients with pT1-3, pN0-3 and M0 breast cancer. RESULTS Patients <35 years of age (315, 11%) presented a significantly increased risk of recurrence and death [hazards ratio (HR) = 1.65, 95% confidence interval (CI) 1.30-2.10 and HR = 1.78, 95% CI 1.12-2.85, respectively] when compared with older patients (2655, 89%) with similar characteristics of disease. This was true considering patients with Luminal B [HR = 1.62, 95% CI 1.21-2.18 for disease-free survival (DFS) and HR = 2.09, 95% CI 0.96-4.53 for overall survival (OS)] and with Triple Negative (HR = 2.04, 95% CI 1.11-3.72 for DFS and HR = 2.20, 95% CI 1.10-4.41 for OS) breast cancer, observing the highest risk of recurrence in the younger patients with HER2-positive breast cancer (HR = 2.37, 95% CI 1.12-5.02) when compared with older patients. CONCLUSIONS Very young patients with Triple Negative, Luminal B or HER2-positive breast cancer have a worse prognosis when compared with older patients with similar characteristics of disease.

237P CMF-likeN % AnthracyclinesN % Anthra and TaxanesN % TaxanesN % Total Not Classified 9 14.8 26 42.6 23 37.7 3 4.9 61 ER+ HER2+ Ki67>19 4 3.7 57 53.3 43 40.2 3 2.8 107 ER+ HER2+ Ki67<20 3 5.8 22 42.3 27 51.9 0 0.0 52 ER+ HER2Ki67>19 26 9.7 131 48.7 101 37.5 11 4.1 269 ER+ HER2Ki67<20 29 10.1 137 47.9 106 37.1 14 4.9 286 ERHER2+ Ki67>19 4 4.9 44 53.7 33 40.2 1 1.2 82 ERHER2+ Ki67<20 0 0.0 10 58.8 7 41.2 0 0.0 21 ERHER2Ki67<20 3 11.1 13 48.1 9 33.3 2 7.4 27 ERHER2Ki67>19 16 10.0 80 50.0 57 35.6 7 4.4 160 Total 94 8.9 520 49.0 406 38.3 41 3.9 1061 Volume 21 | Supplement 8 | October 2010 doi:10.1093/annonc/mdq516 | viii85 Annals of Oncology abstracts