Improved prognosis of young patients with breast cancer undergoing breast-conserving surgery.

BACKGROUND: The aim of the present study was to evaluate how breast cancer prognosis has evolved over time in young women treated with breast-conserving surgery (BCS). METHODS: Data from patients younger than 40 years who had BCS and whole-breast radiotherapy in a single cancer centre between 1997 and 2010 were analysed. The patients were followed until 2016. Endpoints were local recurrence, any breast cancer-related event and death from any cause. RESULTS: A total of 1331 patients were included in the study. After a median follow-up of 9·3 years, 114 local recurrences, 289 breast cancer-related events and 138 deaths had occurred. Women were divided into three groups of similar size based on tertiles of the date of diagnosis: 1997-2002 (524 patients), 2003-2005 (350) and 2006-2010 (457). The risk of local recurrence was 1·42 per 100 person-years in women diagnosed in the first interval, 0·85 per 100 person-years in the second and 0·48 per 100 person-years in the third (P for trend = 0·028). The respective values were 3·01, 2·52 and 2·07 per 100 person-years for any breast cancer-related event (P = 0·004), and 1·59, 1·22 and 0·64 per 100 person-years for death (P = 0·003). Each passing year was associated with a decreasing risk of local recurrence (hazard ratio (HR) 0·93, 95 per cent c.i. 0·87 to 1·00), any breast cancer-related event (HR 0·94, 0·91 to 0·98) and death (HR 0·89, 0·83 to 0·94). A major improvement in prognosis was observed after 2005, when the classification of breast cancer molecular subtypes and use of trastuzumab were implemented in routine clinical practice. CONCLUSION: In the past two decades, both local control and overall prognosis have improved significantly in young women (aged less than 40 years) with breast cancer who undergo BCS.

The prevalence and clinical relevance of tumor-infiltrating lymphocytes (TILs) in ductal carcinoma in situ of the breast.

Background: Tumor-infiltrating lymphocytes (TILs) are a robust prognostic adjunct in invasive breast cancer, but their clinical role in ductal carcinoma in situ (DCIS) has not been ascertained. Patients and methods: We evaluated the prevalence and clinical relevance of TILs in a well annotated series of 1488 consecutive DCIS women with a median follow-up of 8.2 years. Detailed criteria for TILs evaluation were pre-defined involving the International Immuno-Oncology Biomarker Working Group. TILs percentage was considered both as a continuous and categorical variable. Levels of TILs were examined for their associations with ipsilateral breast event (IBE), whether in situ or invasive. Results: Of the 1488 patients with DCIS under study, 35.1% had <1%, 58.3% 1-49% and 6.5% ≥50% peri-ductal stromal lymphocytes. The interobserver agreement in TILs evaluation, measured by the intraclass correlation coefficient (ICC) was 0.96 (95% CI 0.95-0.97). At univariable analysis, clinical factors significantly associated with TILs (P ≤0.001) were intrinsic subtype, grade, necrosis, type of surgery. Her-2 positive DCIS were more frequently associated with TILs (24% of patients with TILs ≥50%), followed by the triple negative (11%), Luminal B/Her-2 positive (9%) and Luminal A/B subtypes (1%) (P < 0.0001). We did not find any association between TILs as a continuous variable and the risk of IBEs. Likewise, when patients were stratified by TILs percentage (<1%, between 1% and 49.9%, and ≥50%), no statistically significant association was observed (10-year cumulative incidence of IBEs: 19%, 17.3%, and 18.7% respectively, P = 0.767). Conclusion: TILs occur more frequently in the Her-2 positive DCIS. Although we did not find a significant association between TILs and the 10-year risk of IBE, our data suggest that immunotherapies might be considered in subsets of DCIS patients.

Sentinel node biopsy after neoadjuvant treatment in breast cancer: Five-year follow-up of patients with clinically node-negative or node-positive disease before treatment.

PURPOSE: It is controversial whether sentinel node biopsy (SNB) without axillary dissection (AD) should be performed in cN1/2 breast cancer patients who become cN0 after neoadjuvant treatment, since the false negative rate (FNR) may be unacceptably high. We assessed outcomes to address this issue. METHODS: We retrospectively assessed 396 cT1-4, cN0/1/2 patients, who became or remained cN0 after neoadjuvant treatment and underwent SNB with at least one sentinel node (SN) found, and AD not performed if the SN was negative. RESULTS: After a median follow-up of 61 months (interquartile range 38-82), five-year overall survival was 90.7% (95% CI, 87.7-93.7) in the whole cohort, 93.3% (95% CI, 90.0-96.6) in those initially cN0, and 86.3% (95% CI, 80.6-92.1) in those initially cN1/2 (P = 0.12). Axillary failure occurred in only 1 (0.7%) initially cN1/2 patient who became cN0. In initially cN0 patients, and also initially cN1/2 patients who responded well to neoadjuvant treatment (ypT0/ypTx), SN-negativity was a significant predictor of good outcome, consistent with the known prognostic significance of axillary status, and suggesting that SN status accurately reflected axillary status. By contrast, in initially cN1/2 patients found to be ypT1/2/3, SN status (and whether or not AD was performed) had no influence on survival. CONCLUSIONS: These findings suggest that SNB is acceptable in cN1/2 patients who become cN0 after neoadjuvant therapy.

Oncological results of oncoplastic breast-conserving surgery: Long term follow-up of a large series at a single institution: A matched-cohort analysis.

PURPOSE: Oncoplastic surgery is a well-established discipline that combines conserving treatment for breast cancer with immediate plastic reconstruction. Although widely practiced, the oncologic outcomes of this combined approach are reported only in small series. The aim of the present paper is to assess the safety of oncoplastic surgery for invasive primary breast cancer. METHODS: We compared 454 consecutive patients who underwent an oncoplastic approach between 2000 and 2008 for primary invasive breast tumors (study group) with twice the number of patients who received conservation alone in the same interval time (control group). Disease free survival and overall survival were estimated using the Kaplan-Meier method. The log-rank test was used to assess differences between groups. RESULTS: The median follow-up was 7.2 years. The overall survival is similar within the two groups, being 91.4% and 91.3% at 10-yr in the study group and in the control group respectively. The disease free survival is slightly lower in the oncoplastic group (69 vs.73.1% at 10-yr). The difference is not statistically significant. DISCUSSION: We have compared a large series of primary breast cancer patients that have undergone oncoplastic surgery (454) with a control group (908) and they were followed for a prolonged period of time. It provides the best available evidence to suggest that oncoplastic surgery is a safe and reliable treatment option for the managing of invasive breast cancer.

Clinical validity of tumor-infiltrating lymphocytes analysis in patients with triple-negative breast cancer.

BACKGROUND: Although tumor-infiltrating lymphocytes (TILs) have been associated with a favorable prognosis in triple-negative breast cancer (TNBC) patients, this marker is not currently considered robust enough for entering the clinical practice. In the present study, we assessed the clinical validity of the guidelines recently issued by the International TIL Working Group in a large retrospective series of well-annotated TNBC patients. PATIENTS AND METHODS: TILs were evaluated in all the full-face H&E sections from 897 consecutive TNBC (i.e. tumors with <1% of ER and PgR immunoreactivity and absence of HER2 overexpression or amplification) patients diagnosed and treated at the European Institute of Oncology between 1995 and 2010 (median follow-up 8.2 years, range 6 months to 18 years). All mononuclear cells were evaluated in the stromal area within the borders of the invasive tumor, reported as a percentage value and treated as a continuous variable in survival analysis. RESULTS: The median percentage of TILs was 20%, and 21.9% of the cases had ≥50% (lymphocyte predominant breast cancer, LPBC) TILs. At univariable survival analysis, TILs were a significant predictor of better disease-free survival (DFS), distant disease-free survival (DDFS) and overall survival (OS) (P < 0.0001). Multivariable analysis confirmed that each 10% increase in TILs strongly predicted better survival, independent of patients' age, lymph node status, tumor size, histological grade, peritumoral vascular invasion and Ki-67 labeling index. Patients with LPBC had a 10-year survival rate of 71%, 84% and 96% for DFS, DDFS and OS, respectively. Stratified analysis revealed a positive correlation between TILs and OS across all the subgroups analyzed. CONCLUSION: Our data support the analytical validity of the recently issued TILs evaluation guidelines in the clinical practice.

Angiosarcoma and atypical vascular lesions of the breast: diagnostic and prognostic role of MYC gene amplification and protein expression.

MYC amplification has been reported as a prominent feature of secondary angiosarcomas (SAS). The differential diagnosis between atypical vascular lesion (AVL) and low-grade angiosarcoma (AS) can be occasionally very difficult or even impossible, and MYC amplification status has been pointed as an important diagnostic tool to distinguish cutaneous vascular lesions of the breast. We assessed MYC amplification and protein expression status by fluorescent in situ hybridization (FISH) and immunohistochemistry (IHC), respectively, in 49 patients diagnosed with breast AS, and 30 patients diagnosed with post-radiation AVL of the breast. Clinical and pathological features, and follow-up data were collected, and survival analyses were performed. Among 37 patients with SAS, twenty patients had tumors with high-level MYC amplification and protein overexpression (54 %). None of primary angiosarcomas (PAS) or AVL cases showed MYC amplification or protein expression. Concordance between MYC amplification (FISH) and protein expression (IHC) was 100 % in AVL, PAS, and SAS. Survival analysis of the SAS patients demonstrates that those with MYC amplification had a significantly worse overall survival compared to cases without MYC amplification (P = 0.035). There was a non-significant trend toward a poor disease-free survival between cases with and without MYC amplification (P = 0.155). Our findings show that MYC amplification is a highly specific but poorly sensitive marker for SAS and, therefore, a negative result does not exclude the diagnosis of angiosarcoma. MYC amplification was associated with adverse prognosis, suggesting a prognostic role of MYC amplification status on SAS of the breast.

Risk of subsequent in situ and invasive breast cancer in human epidermal growth factor receptor 2-positive ductal carcinoma in situ.

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.

Second Axillary Sentinel Lymph Node Biopsy for Breast Tumor Recurrence: Experience of the European Institute of Oncology.

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.

Changes in PgR and Ki-67 in residual tumour and outcome of breast cancer patients treated with neoadjuvant chemotherapy.

BACKGROUND: Limited data are available on the prognostic value of changes in the biological features of residual tumours following neoadjuvant therapies in breast cancer patients. PATIENTS AND METHODS: We collected information through the institutional clinical database on all consecutive breast cancer patients treated with neoadjuvant chemotherapy at the European Institute of Oncology (IEO), Milan, Italy, between 1999 and 2011. We selected patients who did not achieve pathological complete response at final surgery. All patients had a pathological evaluation, including ER, PgR, HER2 protein and Ki-67 expression carried out at the IEO both at diagnostic core biopsy and at final surgery. RESULTS: We identified a total of 904 patients. The 5% of patients who were ER positive at diagnostic biopsy had ER-negative residual tumour at final surgery. For PgR expression, 67% of the patients, whose tumours had a PgR >20% at diagnostic biopsy had a PgR <20% at final surgery. The Ki-67 expression changed from >20% to <20% in 40% of the patients. At the multivariate analysis, the decrease of PgR-immunoreactive cells correlated with improved outcome in terms of disease-free survival (DFS) [hazard ratio (HR) 0.73; 95% confidence interval (CI) 0.54-1.00, P 0.046]. In addition, the decrease of Ki-67 expression to <20% of the cells at final surgery was found to be associated with better outcome both in terms of DFS (HR 0.52; 95% CI 0.40-0.68 P < 0.0001) and overall survival (HR 0.45; 95% CI 0.32-0.64, P < 0.0001). CONCLUSION: The decrease of PgR and Ki-67 expression after preoperative chemotherapy has a prognostic role in breast cancer patients with residual disease.

Long-term follow-up of 5262 breast cancer patients with negative sentinel node and no axillary dissection confirms low rate of axillary disease.

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.

A phase-III prevention trial of low-dose tamoxifen in postmenopausal hormone replacement therapy users: the HOT study.

BACKGROUND: Postmenopausal hormone replacement therapy (HRT) relieves menopausal symptoms and may decrease mortality in recently postmenopausal women, but increases breast cancer risk. Low-dose tamoxifen has shown retained activity in phase-II studies. METHODS: We conducted a phase-III trial in 1884 recently postmenopausal women on HRT who were randomly assigned to either tamoxifen, 5 mg/day, or placebo for 5 years. The primary end point was breast cancer incidence. RESULTS: After 6.2 ± 1.9 years mean follow-up, there were 24 breast cancers on placebo and 19 on tamoxifen (risk ratio, RR, 0.80; 95% CI 0.44-1.46). Tamoxifen showed favorable trends in luminal-A tumors (RR, 0.32; 95% CI 0.12-0.86), in HRT users <5 years (RR, 0.35; 95% CI 0.15-0.82) and in women completing at least 12 months of treatment (RR, 0.49; 95% CI 0.23-1.02). Serious adverse events did not differ between placebo and tamoxifen, including, respectively, coronary heart syndrome (6 versus 4), cerebrovascular events (2 versus 5), VTE (2 versus 5) and uterine cancers (3 versus 1). Vasomotor symptoms were 50% more frequent on tamoxifen. CONCLUSIONS: The addition of low-dose tamoxifen to HRT did not significantly reduce breast cancer risk and increased climacteric symptoms in recently postmenopausal women. However, we noted beneficial trends in some subgroups which may deserve a larger study.

Tailoring treatment for ductal intraepithelial neoplasia of the breast according to Ki-67 and molecular phenotype.

BACKGROUND: The post-surgical management of ductal intraepithelial neoplasia (DIN) of the breast is still a dilemma. Ki-67 labelling index (LI) has been proposed as an independent predictive and prognostic factor in early breast cancer. METHODS: The prognostic and predictive roles of Ki-67 LI were evaluated with a multivariable Cox regression model in a cohort of 1171 consecutive patients operated for DIN in a single institution from 1997 to 2007. RESULTS: Radiotherapy (RT) was protective in subjects with DIN with Ki-67 LI ≥ 14%, whereas no evidence of benefit was seen for Ki-67 LI <14%, irrespective of nuclear grade and presence of necrosis. Notably, the higher the Ki-67 LI, the stronger the effect of RT (P-interaction <0.01). Hormonal therapy (HT) was effective in both Luminal A (adjusted hazard ratio (HR)=0.56 (95% CI, 0.33-0.97)) and Luminal B/Her2neg DIN (HR 0.51 (95% CI, 0.27-0.95)). CONCLUSION: Our data suggest that Ki-67 LI may be a useful prognostic and predictive adjunct in DIN patients. The Ki-67 LI of 14% could be a potential cutoff for better categorising this population of women at increased risk for breast cancer and in which adjuvant treatment (RT, HT) should be differently addressed, independent of histological grade and presence of necrosis.

Effect of low-dose tamoxifen after surgical excision of ductal intraepithelial neoplasia: results of a large retrospective monoinstitutional cohort study.

BACKGROUND: Postsurgical treatment of ductal intraepithelial neoplasia (DIN) with standard doses of tamoxifen has not reached a consensus yet. Given positive results of low-dose tamoxifen on breast cancer biomarkers modulation, we analyzed a large cohort of DIN patients treated with low-dose tamoxifen or no treatment as per institutional guidelines. PATIENTS AND METHODS: All consecutive women operated on at the European Institute of Oncology for estrogen receptor (ER)-positive DIN (474 treated with low-dose tamoxifen and 509 untreated patients) were followed up for a median of 7 years. RESULTS: Compared with untreated patients, a significant 30% reduction in breast cancer risk was observed on low-dose tamoxifen with an adjusted hazard ratio (HR) = 0.70 [95% confidence interval (CI) 0.51-0.94], with a greater benefit in postmenopausal (HR = 0.57; 95% CI 0.34-0.94) than in premenopausal women (HR = 0.79; 95% CI 0.54-1.17). Treated patients with ER and progesterone receptor (PgR) >50% DIN had a lower incidence of breast events than untreated ones (HR = 0.61; 95% CI 0.40-0.94), whereas no protective effect has been observed in patients with ER or PgR <50% DIN. Drug discontinuation resulted in a doubled risk of recurrence in premenopausal women only (HR = 1.95; 95% CI 0.98-3.89). No excess of endometrial cancer occurred. CONCLUSIONS: Low-dose tamoxifen is a promising and safe strategy for highly endocrine responsive DIN. Treatment adherence is crucial in premenopausal women. A definitive trial is ongoing.

Evaluation of fat grafting safety in patients with intraepithelial neoplasia: a matched-cohort study.

BACKGROUND: Fat grafting is widely carried out in breast cancer patients to improve quality in breast reconstruction. Recently, in vitro and animal studies have questioned the role of adipose tissues in cancer development. DESIGNS: Matched-cohort study. We analysed: (i) 59 intraepithelial neoplasia patients who had undergone lipofilling, with no recurrence between primary surgery and lipofilling. (ii) A control group of 118 matched patients (two controls per lipofilling patient) with the corresponding recurrence-free intervals. Both groups were also matched for main cancer criteria. A local event (LE) was the primary end point, with follow-up starting from the baseline. RESULTS: Median follow-up was 63 and 66 months from surgery, and 38 and 42 from baseline, for the lipofilling and control groups, respectively; the 5-year cumulative incidence of LE was 18% and 3% (P = 0.02). Ki-67 was the significant factor in univariate survival analysis. A subgroup analysis showed that lipofilling increased the risk of LE in women <50 years, with high grade neoplasia, Ki-67 ≥ 14 or who had undergone quadrantectomy. CONCLUSION: Higher risk of LE was observed in intraepithelial neoplasia patients following lipofilling. Although further studies are required to validate our conclusions, patients belonging to this subgroup should be informed of these results and the potential risks.

Breast cancer subtype approximations and loco-regional recurrence after immediate breast reconstruction.

BACKGROUND: A small but significant proportion of patients with breast cancer (BC) will develop loco-regional recurrence (LRR) after immediate breast reconstruction (IBR). The LRR also varies according to breast cancer subtypes and clinicopathological features. METHODS: We studied 1742 consecutive BC patients with IBR between 1997 and 2006. According to St Gallen conference consensus 2011, its BC approximations were applied to classify BC into five subtypes: estrogen receptor (ER) and/or progesterone receptor (PgR) positive, HER2 negative, and low Ki67 (<14%) [luminal A]; ER and/or PgR positive, HER2 negative and high Ki67(≥ 14%) [luminal B/HER2 negative]; ER and/or PgR positive, any Ki67 and HER2 positive [luminal B/HER2 positive]; ER negative, PgR negative and HER2 positive [HER2 positive/nonluminal]; and ER negative, PgR negative and HER2 negative [triple negative]. Cumulative incidences of LRR were compared across different subgroups by means of the Gray test. Multivariable Cox regression models were applied. RESULTS: Median follow up time was 74 months (range 3-165). The cumulative incidence of LRR was 5.5% (121 events). The 5-year cumulative incidence of LRR was 2.5% for luminal A; 5.0% for luminal B/HER2 negative; 9.8% for luminal B/HER2 positive; 3.8% for HER2 non luminal; and 10.9% for triple negative. On multivariable analysis, tumor size (pT) >2 cm, body mass index (BMI) ≥ 25, triple negative and luminal B/HER2 positive subtypes were associated with increased risk of LRR. CONCLUSION: Luminal B/HER2 positive, triple negative subtypes and BMI ≥ 25 are independent prognostic factors for risk of LRR after IBR.

Progesterone receptor loss identifies Luminal B breast cancer subgroups at higher risk of relapse.

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.

Outcome and clinical-biological characteristics of patients with advanced breast cancer undergoing removal of ovarian/pelvic metastases.

BACKGROUND: Patients with metastatic breast cancer to the ovary, without tumor debulking and after systemic therapy, have a 5-year survival rate < 10%. PATIENTS AND METHODS: We analyzed a series of 37 patients, operated in one institution over 10 years, for both the primary tumor (PT) and ovarian/pelvic metastases (OPM). Estrogen receptors (ER), progesterone receptors (PgR), HER-2 and Ki-67 were determined. RESULTS: Patients were predominantly young: 27 (73%) patients were < 50 years. Average ER/PgR expression did not change significantly between PT (mean ER = 66%, PgR = 35%) and OPM (mean ER = 67%, PgR = 28%). Median time to OPM was 42 months (range 0-176); 5-year OS after OPM was 51% (95% confidence interval 32% to 67%). When combining ER and PgR status, patients with ER > 50% on both PT and OPM and with PgR > 50% on PT and/or OPM (good prognosis, 11 patients) had a better outcome versus0 patients with ER and PgR ≤ 50% on both PT and OPM (bad prognosis, eight patients) and also versus the remaining patients (intermediate prognosis, 18 patients), P value = 0.010. CONCLUSION: Patients with OPM from breast cancer show a favorable prognosis after tumor debulking, whether it was radical or not, especially when a high expression of ER and PgR is present in both PT and OPM.

Prognostic value of Ki-67 labeling index in patients with node-negative, triple-negative breast cancer.

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.

Mastectomy without radiotherapy: outcome analysis after 10 years of follow-up in a single institution.

The aim of this study was to identify the prognostic factors associated with the risk of loco-regional recurrence (LRR) of women undergoing mastectomy and complete axillary dissection without radiotherapy. We analyzed data from 650 women operated between 1997 and 2001 in a single institution. Median follow-up was 10 years. Overall survival was 89.8 % at 5 years and 76.6 % at 10 years. The 10-year cumulative incidence of LRRs was 10.0 % (5.0, 10.5, 15.8, and 18.5 % in patients with 0, 1-3, 4-9, and ≥10 positive lymph nodes (LNs), respectively). Sixty-two (9.5 %) LRRs were observed, 5 (0.8 %) of which occurred in the axillary LNs. Supraclavicular LNs recurrences (n = 16, 2.5 %) occurred more frequently in patients with four or more positive LNs, Ki-67 ≥ 20 % or extensive peritumoral vascular invasion (PVI). At multivariable analysis, nodal status was the only prognostic factor for local events, while nodal status, Ki-67 and PVI were significant prognostic factors for recurrences in the regional LNs. Moreover, within each category of positive LNs, high values of Ki-67 and extensive PVI were associated with the highest risk of LRR while low values of Ki-67 and absence of extensive PVI were associated with the lowest risk of LRR. Women with node-negative tumors have the lowest risk of LRR and represent the group of patients that might benefit the least from radiotherapy. PVI and Ki-67 might help tailoring PMRT indications among patients with positive LNs. Finally, the very low incidence of recurrences in the axillary LNs raises questions about the inclusion of the axilla in the radiation field.