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A Guerrieri-Gonzaga,
M Lazzeroni,
E Botteri,
D Serrano,
N Rotmensz,
M-C Varricchio,
M Cazzaniga,
G Bollani,
S Mora,
C Montefrancesco,
G Pruneri,
G Viale,
M Intra,
V Galimberti, A Goldhirsch,
V Bagnardi,
B Bonanni,
A Decensi
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ABSTRACT: 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 methodsAll 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.ResultsCompared 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.
Annals of Oncology 03/2013; · 6.43 Impact Factor
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M C Kneubil,
J Brollo,
E Botteri,
G Curigliano,
N Rotmensz, A Goldhirsch,
V Lohsiriwat,
A Manconi,
S Martella,
B Santillo,
J Y Petit,
M Rietjens
[show abstract]
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ABSTRACT: 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.
European journal of surgical oncology: the journal of the European Society of Surgical Oncology and the British Association of Surgical Oncology 01/2013; · 2.56 Impact Factor
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G Cancello,
P Maisonneuve,
N Rotmensz,
G Viale,
M G Mastropasqua,
G Pruneri,
E Montagna,
M Iorfida,
M Mazza,
A Balduzzi,
P Veronesi,
A Luini,
M Intra, A Goldhirsch,
M Colleoni
[show abstract]
[hide abstract]
ABSTRACT: 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 methodsWe 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.ResultsPatients 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.
Annals of Oncology 09/2012; · 6.43 Impact Factor
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P Karlsson,
B F Cole,
B H Chua,
K N Price,
J Lindtner,
J P Collins,
A Kovács,
B Thürlimann,
D Crivellari,
M Castiglione-Gertsch,
J F Forbes,
R D Gelber, A Goldhirsch,
G Gruber
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ABSTRACT: Background Rates and risk factors of local, axillary and supraclavicular recurrences can guide patient selection and target for postmastectomy radiotherapy (PMRT). Patients and methods Local, axillary and supraclavicular recurrences were evaluated in 8106 patients enrolled in 13 randomized trials. Patients received chemotherapy and/or endocrine therapy and mastectomy without radiotherapy. Median follow-up was 15.2 years. Results Ten-year cumulative incidence for chest wall recurrence of >15% was seen in patients aged <40 years (16.1%), with ≥4 positive nodes (16.5%) or 0-7 uninvolved nodes (15.1%); for supraclavicular failures >10%: ≥4 positive nodes (10.2%); for axillary failures of >5%: aged <40 years (5.1%), unknown primary tumor size (5.2%), 0-7 uninvolved nodes (5.2%). In patients with 1-3 positive nodes, 10-year cumulative incidence for chest wall recurrence of >15% were age <40, peritumoral vessel invasion or 0-7 uninvolved nodes. Age, number of positive nodes and number of uninvolved nodes were significant parameters for each locoregional relapse site. Conclusion PMRT to the chest wall and supraclavicular fossa is supported in patients with ≥4 positive nodes. With 1-3 positive nodes, chest wall PMRT may be considered in patients aged <40 years, with 0-7 uninvolved nodes or with vascular invasion. The findings do not support PMRT to the dissected axilla.
Annals of Oncology 07/2012; 23(11):2852-2858. · 6.43 Impact Factor
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ABSTRACT: Background To evaluate whether medullary breast cancer has a better prognosis compared with invasive ductal tumors. Methods Among 12 409 patients, 127 were recorded as invasive medullary tumors and 8096 invasive ductal tumors. Medullary and ductal invasive tumors were compared with regard to stage, age at diagnosis, grade, hormone receptor status, peritumoral vascular invasion, and local and systemic treatment. Pattern of relapse, distant recurrence-free interval (DRFI), and overall survival (OS) were determined for both histological groups. Two cohorts were investigated: a full cohort including the pathologist-determined medullary histology without regard to any other tumor features and a cohort restricted to patients with ER-negative grade 3 tumors. Results Fourteen-year DRFI and OS percents for medullary tumors (n = 127) and invasive ductal tumors (n = 8096) of the full cohort were 76% and 64% [hazard ratio (HR) 0.52, P = 0.0005] and 66% and 57% (HR = 0.75, P = 0.03), respectively. For the restricted cohort, 14-year DRFI and OS percents for the medullary (n = 47) and invasive ductal tumors (n = 1407) were 89% and 63% (HR 0.24, P = 0.002) and 74% and 54% (HR = 0.55, P = 0.01), respectively. Competing risk analysis for DRFI favored medullary tumors (HR medullary/ductal = 0.32; 95% confidence interval = 0.13-0.78, P = 0.01). Conclusion Medullary tumors have a favorable prognosis compared with invasive ductal tumors.
Annals of Oncology 06/2012; 23(11):2843-51. · 6.43 Impact Factor
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E Munzone,
E Botteri,
A Esposito,
A Sciandivasci,
D Franchi,
G Pruneri,
N Rotmensz,
G Curigliano,
L Adamoli,
L Bocciolone, A Goldhirsch,
F Nolé
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ABSTRACT: 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.
Annals of Oncology 04/2012; 23(11):2884-90. · 6.43 Impact Factor
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E Botteri,
O Gentilini,
N Rotmensz,
P Veronesi,
S Ratini,
C Fraga-Guedes,
A Toesca,
C Sangalli,
A Del Castillo,
M Rietjens,
G Viale,
R Orecchia, A Goldhirsch,
U Veronesi
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ABSTRACT: 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.
Breast Cancer Research and Treatment 04/2012; 134(3):1221-8. · 4.43 Impact Factor
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K Ribi,
J Aldridge,
K-A Phillips,
A Thompson,
V Harvey,
B Thürlimann,
F Cardoso,
O Pagani,
A S Coates, A Goldhirsch,
K N Price,
R D Gelber,
J Bernhard
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ABSTRACT: In the BIG 1-98 trial objective cognitive function improved in postmenopausal women 1 year after cessation of adjuvant endocrine therapy for breast cancer. This report evaluates changes in subjective cognitive function (SCF).
One hundred postmenopausal women, randomised to receive 5 years of adjuvant tamoxifen, letrozole, or a sequence of the two, completed self-reported measures on SCF, psychological distress, fatigue, and quality of life during the fifth year of trial treatment (year 5) and 1 year after treatment completion (year 6). Changes between years 5 and 6 were evaluated using the Wilcoxon signed-rank test. Subjective cognitive function and its correlates were explored.
Subjective cognitive function and the other patient-reported outcomes did not change significantly after cessation of endocrine therapy with the exception of improvement for hot flushes (P=0.0005). No difference in changes was found between women taking tamoxifen or letrozole. Subjective cognitive function was the only psychosocial outcome with a substantial correlation between year 5 and 6 (Spearman's R=0.80). Correlations between SCF and the other patient-reported outcomes were generally low.
Improved objective cognitive function but not SCF occur following cessation of adjuvant endocrine therapy in the BIG 1-98 trial. The substantial correlation of SCF scores over time may represent a stable attribute.
British Journal of Cancer 04/2012; 106(10):1618-25. · 5.04 Impact Factor
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Elisabetta Munzone,
E Botteri,
A Sciandivasci,
G Curigliano,
F Nolè,
M Mastropasqua,
N Rotmensz,
M Colleoni,
A Esposito,
L Adamoli,
A Luini, A Goldhirsch,
G Viale
[show abstract]
[hide abstract]
ABSTRACT: 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.
Breast Cancer Research and Treatment 04/2012; 134(1):277-82. · 4.43 Impact Factor
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Annals of Oncology 03/2012; 23(5):1371-2. · 6.43 Impact Factor
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F Didier,
P Arnaboldi,
S Gandini,
A Maldifassi, A Goldhirsch,
D Radice,
I Minotti,
B Ballardini,
A Luini,
B Santillo,
M Rietjens,
J Y Petit
[show abstract]
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ABSTRACT: In a retrospective study, we investigated the reasons why women accepted to undergo a nipple sparing mastectomy (NSM) and why women who could not keep their nipple areola complex (NAC) decided to reconstruct it. We intended to investigate whether keeping the NAC plays a psychological role, to state possible advantages of NSM. Between 2004 and 2006, 310 women with NAC sparing and 143 patients with successive NAC reconstruction were mailed a single open-ended question at follow-up 12 months after final breast reconstruction surgery or final NAC reconstruction with tattoo. The purpose was to explore personal motivations that drove women to accept NSM or to perform a NAC tattoo reconstruction. Responses were classified into 11 categories by five reviewers. We performed an analysis of the relative frequency of emerging issues. Socio-demographic and clinical data were collected. Among the patients who responded to the open-ended question, 190 patients preserved their NAC, and 100 patients received postponed NAC reconstruction. Women in the NSM group were significantly younger (P = 0.02), more highly educated (P < 0.0001), and more frequently lived in Northern Italy (P = 0.03). The reasons for accepting NSM were more frequently related to body image satisfaction and integrity of the body (P = 0.002), reduction of psychological distress (P = 0.003), and surgeon's influence (P < 0.0001). Esthetic reasons were highly associated to the control group. These results help us to better understand the psychological impact of NAC sparing versus NAC reconstruction. NSM was accepted because it was perceived as a technique that preserved the integrity of the body, reduced the feeling of mutilation, improved the breast cosmetic results, and reduced psychological distress regarding the loss of the breast.
Breast Cancer Research and Treatment 02/2012; 132(3):1177-84. · 4.43 Impact Factor
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Annals of Oncology 02/2012; 23(2):543-4. · 6.43 Impact Factor
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M Colleoni,
N Rotmensz,
P Maisonneuve,
M G Mastropasqua,
A Luini,
P Veronesi,
M Intra,
E Montagna,
G Cancello,
A Cardillo,
M Mazza,
G Perri,
M Iorfida,
G Pruneri, A Goldhirsch,
G Viale
[show abstract]
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ABSTRACT: The identification of special types of breast cancer might be of value in assessing prognosis and predicting response to therapy.
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.
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).
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.
Annals of Oncology 10/2011; 23(6):1428-36. · 6.43 Impact Factor
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J T Ribeiro,
L T Macedo,
G Curigliano,
L Fumagalli,
M Locatelli,
M Dalton,
A Quintela,
J B C Carvalheira,
S Manunta,
L Mazzarella,
J Brollo, A Goldhirsch
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ABSTRACT: Despite current trend of targeted therapy development, cytotoxic agents are a mainstay of treatment of patients with breast cancer. We reviewed recent advances in cytotoxic therapy for patients with metastatic breast cancer (MBC).
Medline searches were conducted for English language studies using the term 'MBC' and 'cytotoxic drugs'. The data search was restricted to the period 2000-2011.
Several novel cytotoxic compounds, all microtubule inhibitors, have been approved for clinical use in MBC: (i) nab-paclitaxel, reported to improve tumour response and decrease hypersensitivity reactions in comparison with other taxanes; (ii) ixabepilone, shown to have clinical benefit in taxane- and anthracycline-resistant disease and (iii) eribulin, shown to improve overall survival in heavily pre-treated patients, when compared with best available standard treatment. Agents, such as larotaxel, vinflunine, trabectidin and formulations, including cationic liposomal paclitaxel or paclitaxel poliglumex, are currently under evaluation in phase II/III trials.
Toxicity and chemotherapy resistance are still major limitations in the treatment of patients with MBC. Further research into new cytotoxic compounds is needed in order to maximise benefit, whilst minimising toxicity.
Annals of Oncology 09/2011; 23(3):547-55. · 6.43 Impact Factor
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[show abstract]
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ABSTRACT: Over the last 35 years, classical CMF (combination chemotherapy with cyclophosphamide, methotrexate and fluorouracil) has been a milestone in the adjuvant treatment of women with breast cancer. However, after an early burst of success lasted just over 10 years, classical CMF has been supplanted by 'third-generation' regimens containing taxanes and anthracyclines. Questions have been raised in the past years concerning the true effectiveness of adjuvant CMF for specific subgroups of patients and particularly, recent retrospective data support the fact that the CMF might have a role in the treatment of patients with triple-negative breast cancer. One possible justification for supporting this role of CMF may be sought in the mechanism of action of drugs used in the regimen, as triple-negative cells may be sensitive to alkylating agents that cause double-strand breaks in DNA. The lesson learned from the CMF could lead us to identify new combinations of drugs that could include the optimal chemotherapy backbone for triple-negative breast cancer such as platinum compounds or alkylating agents or Poly (ADP-ribose) polymerase inhibitors. In conclusion, although we have learned a lot from the use of CMF, many questions are still open and hopefully stimulate our thinking, as clinicians, leading us to find new and more effective ways to treat breast cancer.
Annals of Oncology 06/2011; 23(2):305-11. · 6.43 Impact Factor
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ABSTRACT: The 12th St Gallen International Breast Cancer Conference (2011) Expert Panel adopted a new approach to the classification of patients for therapeutic purposes based on the recognition of intrinsic biological subtypes within the breast cancer spectrum. For practical purposes, these subtypes may be approximated using clinicopathological rather than gene expression array criteria. In general, systemic therapy recommendations follow the subtype classification. Thus, 'Luminal A' disease generally requires only endocrine therapy, which also forms part of the treatment of the 'Luminal B' subtype. Chemotherapy is considered indicated for most patients with 'Luminal B', 'Human Epidermal growth factor Receptor 2 (HER2) positive', and 'Triple negative (ductal)' disease, with the addition of trastuzumab in 'HER2 positive' disease. Progress was also noted in defining better tolerated local therapies in selected cases without loss of efficacy, such as accelerated radiation therapy and the omission of axillary dissection under defined circumstances. Broad treatment recommendations are presented, recognizing that detailed treatment decisions need to consider disease extent, host factors, patient preferences, and social and economic constraints.
Annals of Oncology 06/2011; 22(8):1736-47. · 6.43 Impact Factor
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E Montagna,
V Bagnardi,
N Rotmensz,
G Viale,
G Renne,
G Cancello,
A Balduzzi,
E Scarano,
P Veronesi,
A Luini,
S Zurrida,
S Monti,
M G Mastropasqua,
L Bottiglieri, A Goldhirsch,
M Colleoni
[show abstract]
[hide abstract]
ABSTRACT: To evaluate the outcome of breast cancer patients after locoregional recurrence (LRR) according to tumor biological features evaluated at first diagnosis and at the time of recurrence.
We collected information on all consecutive breast cancer patients operated at the European Institute of Oncology between 1994 and 2005. The tumor characteristics and subsequent outcome of patients who experienced LRR were analyzed.
Two hundred and seventy nine patients with LRR were identified, 197 and 82 patients with local and regional recurrence respectively. The overall discordance rate between primary cancer and LRR was 9% for estrogen receptor expression, 22% for progesterone receptor and 4% for human epidermal growth factor receptor 2. For patients with regional recurrence, the risk of distant metastasis was significantly higher compared with local relapse in case of late recurrence (hazard ratio [HR] = 2.76; 95% CI 1.31-5.85). Patients with triple-negative breast cancer at LRR experienced a higher risk of subsequent relapse (HR 2.87 [1.67-4.91]) and death (HR 2.00 [1.25-3.19]).
LRR correlates with a high risk of subsequent events and death in particular in patients with triple-negative subtype.
Annals of Oncology 04/2011; 23(2):324-31. · 6.43 Impact Factor
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G Cancello,
P Maisonneuve,
N Rotmensz,
G Viale,
M G Mastropasqua,
G Pruneri,
E Montagna,
S Dellapasqua,
M Iorfida,
A Cardillo,
P Veronesi,
A Luini,
M Intra,
O Gentilini,
E Scarano, A Goldhirsch,
M Colleoni
[show abstract]
[hide abstract]
ABSTRACT: 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.
Breast Cancer Research and Treatment 03/2011; 127(3):713-20. · 4.43 Impact Factor
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Annals of Oncology 02/2011; 22(2):479-80. · 6.43 Impact Factor
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G Viale,
M M Regan,
P Dell'Orto,
M G Mastropasqua,
E Maiorano,
B B Rasmussen,
G MacGrogan,
J F Forbes,
R J Paridaens,
M Colleoni,
I Láng,
B Thürlimann,
H Mouridsen,
L Mauriac,
R D Gelber,
K N Price, A Goldhirsch,
B A Gusterson,
A S Coates
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ABSTRACT: On average, aromatase inhibitors are better than tamoxifen when used as initial or sequential therapy for postmenopausal women with endocrine-responsive early breast cancer. Because there may be contraindications to their use based on side-effects or cost, we investigated subgroups in which aromatase inhibitors may be more or less important.
Breast International Group 1-98 trial randomized 6182 women among four groups comparing letrozole and tamoxifen with sequences of each agent; 5177 (84%) had centrally confirmed estrogen receptor (ER) positivity. We assessed whether centrally determined ER, progesterone receptor (PgR), human epidermal growth factor receptor 2, and Ki-67 labeling index, alone or in combination with other prognostic features, predicted the magnitude of letrozole effectiveness compared with either sequence or tamoxifen monotherapy.
Individually, none of the markers significantly predicted differential treatment effects. Subpopulation treatment effect pattern plot analysis of a composite measure of prognostic risk revealed three patterns. Estimated 5-year disease-free survival for letrozole monotherapy, letrozole→tamoxifen, tamoxifen→letrozole, and tamoxifen monotherapy were 96%, 94%, 93%, and 94%, respectively, for patients at lowest risk; 90%, 91%, 93%, and 86%, respectively, for patients at intermediate risk; and 80%, 76%, 74%, and 69%, respectively, for patients at highest risk.
A composite measure of risk informs treatment selection better than individual biomarkers and supports the choice of 5 years of letrozole for patients at highest risk for recurrence.
Annals of Oncology 02/2011; 22(10):2201-7. · 6.43 Impact Factor
