Laura Adamoli

IEO - Istituto Europeo di Oncologia, Milano, Lombardy, Italy

Are you Laura Adamoli?

Claim your profile

Publications (56)192.1 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: To assess efficacy of bevacizumab in combination with oral chemotherapy in patients with breast cancer with lymphangitic spread to the chest wall (LBC). To identify surrogate biomarkers of response to bevacizumab. We randomly assigned patients to receive bevacizumab plus either sequential or concurrent oral vinorelbine and capecitabine every 3 weeks. The primary endpoint was time to ultimate progression (TTP); the response rate and overall survival (OS) were secondary endpoints. We performed gene expression profiling on baseline tissue samples collected from triple negative LBC. We assessed circulating endothelial cells (CEC), circulating endothelial progenitors (CEP) and circulating pericyte progenitors (CPP). A total of 66 patients were enrolled. There was no difference in TTP (median TTP 5.3 vs. 4.8 months, p = 0.21) and in OS (median OS 15.8 vs 11.9 months; p = 0.25) when comparing concurrent vs sequential treatment, respectively. Response rate was 25% vs 28% in the concurrent vs sequential arm (p = 1.00), respectively. A set of 16 genes predictive of response to bevacizumab was identified. The counts of CEPs and viable CECs below the median value were associated with an improved overall survival: 26.6 vs 9.5 months for CEPs and 22.6 vs 11.0 months for viable CECs, respectively (p = 0.02). Oral chemotherapy and bevacizumab (BEVIX) is an active regimen in patients with LBC. We support the importance of using LBC as a biological model for investigating angiogenesis inhibitors. CECs and CEPs biomarkers have been identified as predictive markers of outcome and warrant further investigation. Copyright © 2015. Published by Elsevier Ltd.
    Breast (Edinburgh, Scotland) 03/2015; 24(3). DOI:10.1016/j.breast.2015.02.036 · 2.58 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Circulating tumor cells (CTCs) represent an independent prognostic factor in metastatic colorectal cancer, while their significance in early stages is still an open issue. The aim of the study is to investigate the role of CTCs in rectal cancer patients undergoing neoadjuvant chemoradiotherapy (CT-RT). In this prospective single institutional study, cT3-4 and/or N+ rectal cancer was treated with neoadjuvant CT-RT. The primary endpoints were as follows: evaluation of CTCs at baseline (t0), after CT-RT (t1), within 7 days after surgery (t2), and at 6 months from surgery (t3) and correlation with main patient/tumor characteristics, CEA, response to neoadjuvant therapy, and disease-free survival (DFS). CTCs were enumerated with the CellSearch System in 22.5 ml peripheral blood. A repeated measure analysis for binary outcome was used to evaluate over time changes in the percentage of CTCs detectable in blood samples. Of the 90 patients enrolled in this study, 85 were eligible consisting of 52 males and 33 females. Median age was 63 years and median follow-up was 38 months. CTCs were available for all patients at t0, for 67 at t1, for 68 at t2, and for 62 at t3. CTCs > 0 were reported on 16 (19 %) at t0, on 5 (7.5 %) at t1, on 6 (9 %) at t2, and on 3 (5 %) at t3 (P value for trend 0.039). Only for CT-RT responders, CTCs reduced from t0 to t1. No statistically significant association was found between CTCs and main patient/tumor characteristics and DFS. Sixteen patients (19 %) had CTCs a parts per thousand yen1 at t0 with reduction in CTC number in case of objective remissions. The proportion of patients with CTCs a parts per thousand yen1 decreased over the time as the therapeutic course proceeded. Much effort should be oriented toward increasing CTC detection rate by enhancing technical tests and achieving better patient characterization.
    International Journal of Colorectal Disease 07/2014; 29(9). DOI:10.1007/s00384-014-1958-z · 2.42 Impact Factor
  • Source
  • Source
  • Source
    Dataset: JACC2010
  • Source
  • Source
  • Source
  • [Show abstract] [Hide abstract]
    ABSTRACT: Estramustine phosphate sodium (EMP) is an oral agent poorly developed-although active-in patients with metastatic breast cancer (MBC). To resume interest in EMP in MBC, we analyzed a retrospective series of consecutive patients with estrogen receptor-positive disease. EMP was given orally at a dose of 140 mg daily. Treatment discontinuation rates due to progressive disease/toxicity and response rates were assessed. Twenty postmenopausal patients with mainly visceral disease were treated with EMP, in five cases in combination with other anticancer drugs. Median numbers of previous chemotherapies and hormonal treatments were six and four, respectively. From the entire cohort, one complete response and four partial responses were observed. The proportions of patients free of progression at 6 and 12 months were 39 and 8 %, respectively. Six patients discontinued EMP, three each for toxicity and adverse events. Good disease control was obtained in heavily pretreated MBC patients receiving EMP. Toxicity was manageable and reversible although treatment discontinuation has to be considered. A prospective study should be encouraged to identify the optimal use of the drug.
    International Journal of Clinical Oncology 04/2014; 20(1). DOI:10.1007/s10147-014-0694-2 · 2.17 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: In a previous study, we found that patients who were offered the possibility of participation in a clinical trial had unexpressed concerns and fears that prevented them from making free or fully knowledgeable choices about their trial participation. In a selected population of patients who were offered participation in a phase I trial, we prospectively investigated whether a face-to-face discussion about their unexpressed fears might lead to a more conscious decision about whether to accept/refuse participation in the trial. After the presentation of the trial, a questionnaire was administered to assess the presence of specific fears. Before the patients decided whether to participate in the trial, they discussed any fears that they had; finally, the impact of the discussion on the patients' choice to participate was evaluated. The majority (86%) of the patients thought that physicians conduct clinical trials for scientific interest, 13% felt exploited as 'guinea pigs' and 20% believed they were offered participation because they had no further hope for improvement. These existing fears were not elicited during the trial interview because the patients were themselves unaware of having them (28%) and because of fear of the doctors (3%). The possibility of discussing these fears was felt as an opportunity and made patients feel more conscious (92%) and freer (97%) when making their choice. Recognising and discussing misconceptions and fears, often unexpressed, make patients freer and more aware when facing the choice of whether or not \to participate in a phase I clinical trial. Copyright © 2013 John Wiley & Sons, Ltd.
    Psycho-Oncology 03/2014; 23(3). DOI:10.1002/pon.3424 · 4.04 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Immunotherapy for the treatment of breast cancer can be categorized as either (a) specific stimulation of the immune system by active immunization, with cancer vaccines, or (b) passive immunization, such as tumor-specific antibodies (including immune modulators) or adoptive cell therapy that inhibit the function of, or directly kill, tumor cells. We will present the current information and the future perspectives of immunotherapy in patients with breast cancer, including the prognostic role of tumor infiltrating lymphocytes, immune signatures, targeted therapies modulating the immune system, and tumor antigen cancer vaccines. Active immunotherapy in breast cancer and its implementation into clinical trials have been largely a frustrating experience in the last decades. The concept that the immune system regulates cancer development is experiencing a new era of interest. It is clear that the cancer immunosurveillance process indeed exists and potentially acts as an extrinsic tumor suppressor. Also, the immune system can facilitate tumor progression by sculpting the immunogenic phenotype of tumors as they develop. Cancer immunoediting represents a refinement of the cancer immunosurveillance hypothesis and resumes the complex interaction between tumor and immune system into three phases: elimination, equilibrium, and escape. Major topics in the field of immunology deserve a response: what do we know about tumor immunogenicity, and how might we therapeutically improve tumor immunogenicity? How can we modulate response of the immune system? Is there any gene signature predictive of response to immune modulators? The success of future immunotherapy strategies will depend on the identification of additional immunogenic antigens that can serve as the best tumor-rejection targets. Therapeutic success will depend on developing the best antigen delivery systems and on the elucidation of the entire network of immune signaling pathways that regulate immune responses in the tumor microenvironment.
    Breast Cancer Research 02/2014; 16(1):204. DOI:10.1186/bcr3620 · 5.33 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: The discordance in oestrogen receptor (ER), progesterone receptor (PgR) and human epidermal growth factor receptor 2 (HER2) status between primary and recurrent breast cancer is being intensively investigated and a large amount of data have been produced. However, results from different studies are heterogeneous and often conflicting. To highlight this issue, a meta-analysis of published data was performed. A literature search was performed using Medline, and all the studies published from 1983 to 2011 comparing changes in ER, PgR and/or HER2 status in patients with matched breast primary and recurrent tumours were included. We used random-effects models to estimate pooled discordance proportions. We selected 48 articles, mostly reporting retrospective studies. Thirty-three, 24 and 31 articles were focused on ER, PgR and HER2 changes, respectively. A total of 4200, 2739 and 2987 tumours were evaluated for ER, PgR and HER2 discordance, respectively. The heterogeneity between study-specific discordance proportions was high for ER (I(2)=91%, p<0.0001), PgR (I(2)=79%, p<0.0001) and HER2 (I(2)=77%, p<0.0001). Pooled discordance proportions were 20% (95% confidence interval (CI): 16-35%) for ER, 33% (95% CI: 29-38%) for PgR and 8% (95% CI: 6-10%) for HER2. Pooled proportions of tumours shifting from positive to negative and from negative to positive were 24% and 14% for ER (p=0.0183), respectively. The same figures were 46% and 15% for PgR (p<0.0001), and 13% and 5% for HER2 (p=0.0004). Our findings strengthen the concept that changes in receptor expression may occur during the natural history of breast cancer, suggesting clinical implications and a possible impact on treatment choice.
    European journal of cancer (Oxford, England: 1990) 11/2013; 50(2). DOI:10.1016/j.ejca.2013.10.004 · 4.82 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Five to 10% of women with newly diagnosed breast cancer have synchronous metastases (de novo stage IV). A further 20% will develop metastases during follow-up (recurring stage IV). We compared the clinical outcomes of women with HER2-positive metastatic breast cancer (MBC) receiving first-line trastuzumab-based therapy according to type of metastatic presentation. Retrospective analysis of 331 MBC patients receiving first-line trastuzumab-based treatment. Response rates (RR) were compared by the chi-square test. Time-to progression (TTP) and overall survival (OS) curves were compared by the log-rank test. Cox-proportional hazards models were used to study predictors of PFS and OS, including the type of metastatic presentation. Seventy-seven patients (23%) had de novo stage IV disease. Forty-six of these patients underwent surgery of the primary ("de novo/surgery"). Response rates to first-line trastuzumab-based therapy and median progression-free survival did not differ in patients with "recurring", "de novo/surgery" and "de novo" without surgery ("de novo/no surgery) stage IV breast cancer. However, women with "de novo/surgery" stage IV breast cancer had the longest median OS (60 months), and those with "de novo/no surgery" stage IV breast cancer the shortest (26 months). For women with recurring metastatic breast cancer median OS was 40 months (overall log-rank test, p < 0.01). Multivariate analysis confirmed these findings. Our analysis shows that response rates and PFS to first-line trastuzumab-based therapy do not differ significantly between de novo and recurring stage IV, HER2 positive breast cancer. The observed difference in OS favoring women with de novo stage IV disease submitted to surgery of the primary tumor could be the result of a selection bias.
    Breast (Edinburgh, Scotland) 11/2013; DOI:10.1016/j.breast.2013.10.005 · 2.58 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Beta-blockers (BB) drugs have been used for decades worldwide, mainly to treat hypertension. However, in recent epidemiological studies, BBs were suggested to improve cancer prognosis. In the wake of this evidence, we evaluated the possible therapeutic effect of BBs in triple-negative breast cancer (TNBC) patients. We identified 800 postmenopausal women operated between 1997 and 2008 for early primary TNBC. The effect of BB intake on the risk of breast cancer (BC) recurrence and death was evaluated through competing risk and Cox regression survival models. At cancer diagnosis, 74 (9.3 %) women out of 800 were BBs users. Median age was 62 years in BB users and 59 years in non-users (P = 0.02). BB users and non-users were similarly distributed by all tumor characteristics. The 5-year cumulative incidence of BC-related events was 13.6 % in BB users and 27.9 % in non-users (P = 0.02). The beneficial impact of BBs remained statistically significant at multivariable analysis (HR, 0.52; 95 % CI 0.28-0.97), after the adjustment for age, tumor stage, and treatment, peritumoral vascular invasion and use of other antihypertensive drugs, antithrombotics, and statins. Adjusted HRs for metastases and for BC deaths were 0.32 (95 % CI 0.12-0.90) and 0.42 (95 % CI 0.18-0.97), respectively, in favor of BBs. Hypertension, other antihypertensive drugs, antithrombotics, and statins did not impact prognosis. In this series of postmenopausal TNBC patients, BB intake was associated with a significantly decreased risk of BC-related recurrence, metastasis, and BC death. Innovative therapeutic strategies including BBs should be urgently explored in cancer patients.
    Breast Cancer Research and Treatment 08/2013; 140(3). DOI:10.1007/s10549-013-2654-3 · 4.20 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Despite improvements in brain surgery and radiotherapy, patients with brain metastases (BM) from breast cancer still have a poor prognosis. The aim of the present study is to evaluate the outcome of a multimodal therapeutic strategy in an unselected cohort of patients. We retrospectively reviewed 24 breast cancer patients who developed BM and were treated with brain surgery, radiotherapy, and/or systemic therapy in the same institutions. Primary treatment for BM was surgery in the whole cohort, radiotherapy in 11 patients, radiotherapy combined with systemic therapy in nine patients, and systemic therapy as single treatment in six patients (chemo/targeted therapy n= 4; hormonal therapy n=2). The median time from breast cancer diagnosis to brain surgery was 57.6 months (range 1.8-130.7 months). The overall survival from surgery for BM was 22 months and the overall survival from BM surgery by presence of other metastatic sites at surgery was 25 months for patients with BM only and 11 months for patients with other metastatic sites (p=0.046). Although this study is retrospective and limited by the small number of patients, the overall survival of 22 months from the time of brain surgery represents an excellent outcome. The multidisciplinary approach that combines the efforts of specialists from different disciplines leads to satisfactory results for patients in terms of survival in the current clinical practice and prospective subtype-oriented trials are urgently required in this category of patients.
    ecancermedicalscience 04/2013; 7:309. DOI:10.3332/ecancer.2013.309 · 1.20 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: The impact of breast surgery on survival of metastatic breast cancer (MBC) patients is controversial. We addressed the question in a mono-institutional series of MBC patients with synchronous bone metastases. We identified 187 consecutive women diagnosed between 2000 and 2008 with locally operable (T1-T3) MBC, synchronous bone metastases, with no other distant sites being involved. Progression-free survival (PFS) and overall survival (OS) were compared between operated and non-operated patients. Median age was 51 years; 92 % of the women had a hormone-positive tumor. At the time of diagnosis, 131 patients out of 187 (70 %) underwent surgery. Operated and non-operated patients differed in terms of number of bone metastatic sites: a single metastasis was detected in 35 (28 %) operated, and 6 (11 %) non-operated cases (P = 0.01). No other significant differences were observed. The multi-adjusted hazard ratio was 0.63 (95 % CI 0.43-0.92) for PFS and 0.64 (95 % CI 0.41-0.99) for OS in favor of surgery. The 5-year cumulative incidence of ipsilateral breast skin progressions among non-operated patients was 18 %. In this large and homogeneous series of MBC patients with synchronous bone metastases, the role of breast surgery had a favorable impact on both disease progression and mortality.
    Breast Cancer Research and Treatment 02/2013; 138(1):303-10. DOI:10.1007/s10549-013-2449-6 · 4.20 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Breast cancer is a heterogeneous disease. Circulating tumor cell (CTC) enumeration might be useful to identify different risk categories within each molecular subtype. We retrospectively analyzed 203 consecutive patients with metastatic breast cancer with baseline CTC enumeration performed with CellSearch (Veridex Corp, Warren, NJ) between March 2005 and July 2011. Patients were categorized into 3 prognostic groups based on the number of CTCs (0, 1-4, and ≥ 5) and into 5 categories based on tumor biological characteristics: luminal-A (estrogen receptor [ER] and progesterone receptor [PR] > 1%, grade 1/2, human epidermal growth factor 2 [HER2]-negative [HER2(-)], Ki67 value < 14%); luminal-B (ER and/or PR > 1%, grade 3, HER2(-), Ki67 value > 14%); luminal-B HER2-positive [HER2(+)] (ER and/or PR > 1%, any grade, HER2(+), Ki-67 value any); HER2(+) (HER2 overexpressed/fluorescence in situ hybridization [FISH] amplified, ER and PR absent); triple negative (TN) (ER and PR 0%, HER2 not overexpressed/FISH not amplified). Median age was 57 years (range 31-78 years). Twenty-seven patients (13.3%) had luminal-A category, 105 (51.7%) patients had luminal-B, 29 (14.3%) patients had luminal-B HER2(+), 24 patients (11.8%) had HER2(+), and 18 patients (8.9%) had TN. CTCs were mostly found in patients with luminal-A/luminal-B HER2(-) subtype. At multivariable analysis, CTC count was a significant predictive factor for overall survival (OS) in all molecular subtypes (log-rank P < .01). Patients with 0 CTCs/7.5 mL blood and all subtypes, except HER2(+), seem to perform better compared with other categories. These findings confirm CTCs as an important prognostic factor for metastatic breast cancer in all molecular subtypes. Larger studies could help identify metastatic breast cancer subgroups in which CTC analysis would be particularly useful.
    Clinical Breast Cancer 10/2012; 12(5):340-6. DOI:10.1016/j.clbc.2012.07.001 · 2.63 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Fulvestrant is effective in postmenopausal women with estrogen receptor-positive advanced breast cancer (ABC). So far, no published data exist on fulvestrant combined with chemotherapy. We retrospectively assessed the role of combining oral metronomic cyclophosphamide and methotrexate (CM) to fulvestrant in two cohorts (A and B) of heavily pre-treated estrogen receptor-positive advanced ABC patients. From October 2006 to September 2009, 33 postmenopausal patients received fulvestrant 250 mg via i.m. injection q28 days. In A, 20 patients added metronomic cyclophosphamide (50 mg p.o. daily) and methotrexate (2.5 mg p.o. twice daily on day 1 and day 4 weekly) after disease progression, continuing fulvestrant at the same dose. In B, 13 patients started fulvestrant plus metronomic CM upfront. Thirty-two patients were evaluable for response. Clinical benefit (partial response + stable disease >24 months) for A + B was 56% (95% CI 38-74%). The addition of metronomic CM did not determine relevant toxicities. Treatment with fulvestrant plus metronomic CM was effective in advanced ABC and was minimally toxic providing long-term disease control in a high proportion of patients. The prolonged clinical benefit, often desirable in such patients, supports this regimen as an additional and useful therapeutic tool.
    The Breast Journal 07/2012; 18(5):470-4. DOI:10.1111/j.1524-4741.2012.01278.x · 1.43 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: The efficacy of trastuzumab beyond metastatic disease progression (PD) is controversial. We retrospectively analyzed 213 patients with HER2-positive metastatic breast cancer treated with trastuzumab-based therapies between November 1998 and December 2010. Out of 213 patients, 134 (58%) had received trastuzumab consecutively for at least 1 year and 154 of 213 patients (67%) had received two or more lines of consecutive trastuzumab-based therapy beyond PD. For these subgroups of patients, we examined the correlation between patients' survival and time to first tumor progression (TTP). Among 134 patients who received trastuzumab for at least 1 year, 66 (49%) never had PD within the first year of treatment, whereas 68 (51%) had PD at least once within the first year. The estimated 2-year overall survival (OS) after 1 year was 82% for those who had no PD during the first year (median OS 5.1 years) and 70% for those who had PD (median OS 2.6 years) (P<0.0001). Among 154 patients who received two or more lines of consecutive trastuzumab-based therapy beyond PD, we calculated a median first TTP of 8.7 months. In terms of survival after first progression, patients with a longer first TTP (≥8.7 months) had better survival compared with those who had a shorter first TTP (39 months, 95% CI 31-63; vs. 28 months, 95% CI 22-32; P=0.0004). T-based therapy was well tolerated and only five patients experienced a cardiac event. Our retrospective data suggest that treatment with trastuzumab beyond progression is a viable option for patients with advanced HER2-positive breast cancer, whose disease has progressed on previous trastuzumab-based regimens.
    Anti-cancer drugs 07/2012; 23(10):1089-98. DOI:10.1097/CAD.0b013e32835679d3 · 1.89 Impact Factor
  • [Show abstract] [Hide abstract]
    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. DOI:10.1093/annonc/mds098 · 6.58 Impact Factor

Publication Stats

489 Citations
192.10 Total Impact Points

Institutions

  • 2006–2013
    • IEO - Istituto Europeo di Oncologia
      • Department of Medical Oncology
      Milano, Lombardy, Italy
  • 2012
    • Università degli Studi di Milano-Bicocca
      Milano, Lombardy, Italy
  • 1984–2009
    • University of Milan
      • Institute of Medical Statistics and Biometry "G. A. Maccacaro" IBSUM
      Milano, Lombardy, Italy
  • 1991–1997
    • Azienda Ospedaliera San Gerardo
      Monza, Lombardy, Italy