ABSTRACT
PURPOSE: In Italy, Lombardy was the first region to reimburse multigene assays (MGAs) for patients otherwise candidates for chemotherapy. This is a real-world experience of MGAs usage in six referral cancer centers in Lombardy. METHODS: Among MGAs, Oncotype DX (RS) was used in 97% of cases. Consecutive patients tested with Oncotype DX from July 2020 to July 2022 were selected. The distribution of clinicopathologic features by RS groups (low RS: 0-25, high RS: 26-100) was assessed using chi-square and compared with those of the TAILORx and RxPONDER trials. RESULTS: Out of 1,098 patients identified, 73% had low RS. Grade and Ki67 were associated with RS (p < 0.001). In patients with both G3 and Ki67 > 30%, 39% had low RS, while in patients with both G1 and Ki67 < 20%, 7% had high RS. The proportion of low RS in node-positive patients was similar to that in RxPONDER (82% vs 83%), while node-negative patients with low RS were significantly less than in TAILORx (66% vs 86%, p < 0.001). The distribution of Grade was different from registration trials, with more G3 and fewer G1 (38% and 3%) than in TAILORx (18% and 27%) and RxPONDER (10% and 24%) (p < 0.001). Patients ≤ 50 years were overrepresented in this series (41%) than in TAILORx and RxPONDER (31% and 24%, respectively) (p < 0.001) and, among them, 42% were node positive. CONCLUSIONS: In this real-world series, Oncotype DX was the test almost exclusively used. Despite reimbursement being linked to pre-test chemotherapy recommendation, almost 3/4 patients resulted in the low-RS group. The significant proportion of node-positive patients ≤ 50 years tested indicates that oncologists considered Oncotype DX informative also in this population.
Subject(s)
Biomarkers, Tumor , Breast Neoplasms , Humans , Female , Breast Neoplasms/genetics , Breast Neoplasms/drug therapy , Breast Neoplasms/pathology , Middle Aged , Aged , Biomarkers, Tumor/genetics , Italy , Adult , Gene Expression Profiling/methods , Clinical Trials as Topic , Ki-67 Antigen/genetics , Ki-67 Antigen/metabolism , Neoplasm GradingABSTRACT
The increasing understanding of breast cancer biology has provided the basis for the development of multigene signatures aimed to improve the capability of clinicians to assess patients' prognostication and risk stratification. Incorporating these tools in clinical practice has profoundly impacted on the decision-making process for the adjuvant therapy of patients with ER+/HER2- early breast cancer and the results from prospective adjuvant trials have strengthened the clinical utility of multigene signatures in this setting. In July 2019, Lombardy was the first Region in Italy to reimburse genomic testing for patients with ER+/HER2- early breast cancer. Three years later, a group of investigators from six referral Cancer Centers in Lombardy convened to debate the use of multigene signatures in clinical practice and share their own experience with the tests after reimbursement. Here, we reviewed relevant data on the role of multigene signatures in tailoring adjuvant chemotherapy for patients with ER+/HER2- early breast cancer and discussed about the optimal use of these assays in current clinical practice. As the treatment landscape of early breast cancer evolves and novel questions about the possible additional applications of multigene assays arise, we also provide our viewpoint on the potential implementation of the assays in the evolving scenario ER+/HER2- early breast cancer treatment.
ABSTRACT
BACKGROUND: Adjuvant chemotherapy for Luminal B-like breast cancers usually includes anthracycline-based regimens. However, some patients are reluctant to receive chemotherapy because of side-effects, especially alopecia, and ask for a "less intensive" or personalized approach. PATIENTS AND METHODS: We conducted a phase II feasibility trial to evaluate pegylated liposomal doxorubicin (PLD, Caelyx®) as adjuvant chemotherapy. Patients who received surgery for pT1-3, any N, and luminal B-like early-stage breast cancer (EBC) candidates for adjuvant chemotherapy were included. PLD was administered intravenously at 20 mg/m2 biweekly for eight courses. Endocrine therapy was given according to menopausal status. Trastuzumab was administered in HER2-positive disease. The primary endpoint was to evaluate the feasibility of this regimen, defined as the ability of a patient to achieve a relative dose intensity (RDI) of at least 85% of the eight cycles of treatment. Secondary endpoints included adverse events (AEs), tolerability, breast cancer-free survival, disease-free survival, and overall survival. RESULTS: From March 2016 to July 2018, 63 patients were included in the trial. Median age was 49 years (range: 33-76), with mostly pre- and peri-menopausal (65%) and stage I-II (94%). Only 5% of patients had HER2-positive EBC. Median RDI was 100% (range: 12.5-100%; interquartile range, IQR: 87.5-100%). The proportion of patients meeting the primary endpoint was 84% (95% confidence interval, CI: 73-92%). Overall, 55 out of 63 enrolled patients completed treatment (87%, 95% CI: 77-94%). Most common AEs were palmar-plantar erythrodysesthesia (12.2%), fatigue (10.4%), and mucositis (8.5%). Only 13% of patients had G3 AEs. None had alopecia. After a median follow-up of 3.9 years (range: 0.3-4.7) two distant events were observed, and all patients were alive at the date of last visit. CONCLUSIONS: The trial successfully met its primary endpoint: the regimen was feasible and well tolerated and could be considered for further evaluation as a treatment option for patients with contraindications to standard anthracyclines or requiring a personalized, less intensive approach.
Subject(s)
Breast Neoplasms , Breast Neoplasms/drug therapy , Doxorubicin/analogs & derivatives , Feasibility Studies , Female , Humans , Middle Aged , Polyethylene GlycolsABSTRACT
The development of CDK 4/6 inhibitors has dramatically changed the therapeutic management of hormone receptor-positive (HR+) and HER2 negative metastatic breast cancer (MBC). In combination with fulvestrant, palbociclib, ribociclib and abemaciclib have each been approved for HR+/HER2- MBC following the results of randomized Phase III studies (PALOMA-3, MONALEESA-3, MONARCH-2) and shown a significant advantage in PFS. Data from clinical trials support the combination with aromatase inhibitors in the first line setting and with fulvestrant in the second line. Each agent is well tolerated, and most of the toxicities observed with this class of drugs are generally easily manageable and free from particular complications. The latest evidence from MONARCH-2 and MONALEESA-3 trials shows benefits in terms of overall survival (OS), suggesting an option of using fulvestrant in combination with CDK 4/6 inhibitors in the first line setting. Additional research is needed to determine optimal treatment sequencing, understand the mechanisms of resistance, and develop novel therapeutic strategies to overcome clinical resistance and further improve the outcomes of patients with HR+/HER- MBC. Key questions in the field include the further impact on progression-free survival, overall survival, and the role of continuing CDK 4/6 blockade beyond progression. The purpose of this review is to describe the clinical relevance of fulvestrant in combination with CDK 4/6 inhibitors in HR+/HER2- MBC patients, as well as to discuss the current controversies and evolving research areas.
ABSTRACT
Multiple synchronous (multifocal or multicentric) ipsilateral breast cancers with heterogeneous histopathology are a rare clinical occurrence, however, their incidence is increasing due to the use of MRI for breast cancer screening and staging. Some studies have demonstrated poorer clinical outcomes for this pattern of breast cancer, but there is no evidence to guide clinical practice. In this multidisciplinary review, we reflect on pathology and molecular characteristics, imaging findings, surgical management including conservation and reconstructive options and approach to the axilla, and the role of chemotherapy and radiotherapy. Multidisciplinary discussions appear decisive in planning an appropriate surgical choice and defining the correct systemic treatment tailored to each clinical condition.
Subject(s)
Breast Neoplasms/diagnosis , Tumor Burden , Breast Neoplasms/etiology , Breast Neoplasms/mortality , Breast Neoplasms/therapy , Combined Modality Therapy , Disease Management , Disease Susceptibility , Female , Genetic Predisposition to Disease , Humans , Lymphoscintigraphy , Multimodal Imaging/methods , Neoplasm Grading , Neoplasm Staging , Prognosis , Retreatment , Sentinel Lymph Node Biopsy , Treatment OutcomeABSTRACT
BACKGROUND: Chemotherapy-induced alopecia (CIA) is a distressing side effect of cancer therapy. The trial aimed to assess feasibility and effectiveness of scalp-cooling system DigniCap® to prevent CIA in primary breast cancer patients receiving an anthracycline containing adjuvant chemotherapy (CT). METHODS: Hair loss (HL) was evaluated by patient self-assessment and by the physician according to the Dean's scale at baseline and after each cycle of CT. The primary efficacy endpoint was the patient self-assessment HL score evaluated at least 3 weeks after completing CT. A Dean's scale score of 0-2 (i.e. HL ≤50%) was considered a success. RESULTS: From July 2014 to November 2016, 139 consecutive breast cancer patients were enrolled and received at least one treatment with scalp cooling. Fifty-six out of 131 evaluated patients successfully prevented HL (43%, 95% CI: 34-51%). Twenty-four patients (32%) discontinued the scalp cooling because of alopecia or scalp-cooling related AE, three patients had missing information on CIA, and 48 patients (64%) had a HL greater than 50% after CT. No serious AEs were reported. CONCLUSIONS: DigniCap® System resulted as a promising medical device to be safely integrated in supportive care of early breast cancer patients. Longer follow-up is needed to assess long-term safety and feasibility. CLINICAL TRIAL REGISTRATION NUMBER: NCT03712696.
Subject(s)
Alopecia/prevention & control , Anthracyclines/adverse effects , Breast Neoplasms/drug therapy , Adult , Aged , Alopecia/chemically induced , Breast Neoplasms/psychology , Cold Temperature , Female , Humans , Middle Aged , Prospective Studies , Quality of Life , ScalpABSTRACT
This study investigates the impact of whole-body MRI (WB-MRI) in addition to CT of chest-abdomen-pelvis (CT-CAP) and 18F-FDG PET/CT (PET/CT) on systemic treatment decisions in standard clinical practice for patients with advanced breast cancer (ABC). WB-MRI examinations in ABC patients were extracted from our WB-MRI registry (2009-2017). Patients under systemic treatment who underwent WB-MRI and a control examination (CT-CAP or PET/CT) were included. Data regarding progressive disease (PD) reported either on WB-MRI or on the control examinations were collected. Data regarding eventual change in treatment after the imaging evaluation were collected. It was finally evaluated whether the detection of PD by any of the two modalities had induced a change in treatment. Among 910 WB-MRI examinations in ABC patients, 58 had a paired control examination (16 CT-CAP and 42 PET/CT) and were analysed. In 23/58 paired examinations, additional sites of disease were reported only on WB-MRI and not on the control examination. In 17/28 paired examinations, PD was reported only on WB-MRI and not on the control examination. In 14 out of the 28 pairs of examinations that were followed by a change in treatment, PD had been reported only on WBMRI (14/28; 50%), while stable disease had been reported on the control examination. In conclusion, WB-MRI disclosed PD earlier than the control examination (CT-CAP or PET/CT), and it was responsible alone for 50% of all changes in treatment.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Bone Neoplasms/diagnostic imaging , Breast Neoplasms/diagnostic imaging , Magnetic Resonance Imaging/methods , Whole Body Imaging/methods , Adult , Aged , Bone Neoplasms/prevention & control , Bone Neoplasms/secondary , Breast/diagnostic imaging , Breast/pathology , Breast Neoplasms/drug therapy , Breast Neoplasms/pathology , Disease Progression , Feasibility Studies , Female , Fluorodeoxyglucose F18/administration & dosage , Humans , Middle Aged , Patient Selection , Positron Emission Tomography Computed Tomography/methods , Radiopharmaceuticals/administration & dosage , Retrospective Studies , Sensitivity and Specificity , Treatment OutcomeABSTRACT
BACKGROUND: Few data are available on the benefit of metronomic cyclophosphamide, capecitabine, and vinorelbine as first-line therapy in patients with metastatic triple-negative breast cancer. METHODS: This phase II study assessed the safety and efficacy of metronomic oral chemotherapy with vinorelbine 40 mg orally 3 times a week, cyclophosphamide 50 mg daily, and capecitabine 500 mg 3 times a day (VEX regimen) in untreated metastatic triple-negative breast cancer patients. The biopsy of the metastatic site had to be triple-negative, independent of the hormone receptor expression of the primary tumor. The primary endpoint was time to progression (TTP). Secondary endpoints included assessment of safety and clinical benefit (objective response rate plus stable disease rate at ≥24 weeks). RESULTS: 25 patients were included, and 22 were evaluable for both efficacy and toxicities (median age, 66 years). Median TTP was 6.4 months (95% confidence interval 3.6-12.6). The most common grade 1-2 toxicities were nausea, diarrhea, leuko-/neutropenia, and reversible liver enzyme alteration. Grade 3 events included hand and foot syndrome (9%). CONCLUSION: The VEX regimen demonstrated activity and was relatively well tolerated when given as first-line therapy in selected metastatic breast cancer patients with triple-negative disease.
ABSTRACT
BACKGROUND: Inflammatory breast cancer (IBC) is a rare and highly aggressive disease. A neoadjuvant regimen with chemotherapy and an antiangiogenic strategy was investigated. PATIENTS AND METHODS: Patients with primary or recurrent IBC who were candidates for neoadjuvant treatment received weekly carboplatin and paclitaxel plus bevacizumab every 3 weeks and oral metronomic cyclophosphamide for 6 months. Trastuzumab was added for patients with HER2+ tumors and endocrine therapy was added for patients with estrogen receptor and/or progesterone receptor ≥ 10% tumors. Oral metronomic capecitabine and cyclophosphamide was continued for 6 months after surgery in those patients with a response. The primary efficacy endpoints were pathologic complete remission (pCR) and the objective response. RESULTS: From July 2010 to December 2013, 34 patients with IBC were included. The surrogate intrinsic tumor subtypes were as follows: luminal B-like (HER2-), 10 (29%); luminal B-like (HER2+), 8 (24%); HER2+ (nonluminal), 6 (18%); and triple negative, 10 (29%). An objective response was obtained in 30 patients (88%; 95% confidence interval, 73%-97%) and a pCR in 10 patients (29%; 95% confidence interval, 15%-48%). The proportion of pCR was significantly greater in the patients with HER2+ tumors (57%) than in patients with triple-negative (20%) or luminal B-like (HER2-) tumors (0%; P = .019). After a median follow-up of 4.4 years, the 5-year disease-free survival and overall survival was 58% and 72%, respectively. The achievement of pCR was associated with longer disease-free (P = .12) and overall (P = .029) survival. CONCLUSION: In patients with IBC, neoadjuvant treatment with the investigated regimen was successful and well tolerated. Further studies evaluating the potential benefit of an antiangiogenic strategy in this setting are awaited.
Subject(s)
Angiogenesis Inhibitors/administration & dosage , Antineoplastic Agents, Immunological/administration & dosage , Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Bevacizumab/administration & dosage , Inflammatory Breast Neoplasms/drug therapy , Neoadjuvant Therapy/methods , Angiogenesis Inhibitors/adverse effects , Antineoplastic Agents/administration & dosage , Antineoplastic Agents/adverse effects , Antineoplastic Agents, Immunological/adverse effects , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Bevacizumab/adverse effects , Biomarkers, Tumor/metabolism , Drug Administration Schedule , Female , Follow-Up Studies , Humans , Inflammatory Breast Neoplasms/mortality , Inflammatory Breast Neoplasms/pathology , Middle Aged , Neoadjuvant Therapy/adverse effects , Survival Analysis , Treatment OutcomeABSTRACT
In a phase II study we assessed the safety and efficacy of metronomic oral chemotherapy with vinorelbine, cyclophosphamide capecitabine in patients with metastatic breast cancer, either as first-line (naïve group) or second-line or greater therapy (pre-treated group). Eligible patients had histologically or cytologically proven, hormone-receptor positive metastatic breast cancer. The primary end point was median time to progression (TTP). A total of 43 patients in the naïve group and 65 in the pre-treated group were enrolled. The median TTP was 25.1 months in the naïve group and 11.2 months in the pre-treated group. The most frequently reported grade 2 treatment-related adverse events were leukopenia and hand and foot syndrome. Metronomic combination of cyclophosphamide, capecitabine and vinorelbine showed significant activity and good tolerability in patients hormonal receptor positive, metastatic breast cancer patients.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Breast Neoplasms/drug therapy , Capecitabine/administration & dosage , Cyclophosphamide/administration & dosage , Vinblastine/analogs & derivatives , Administration, Metronomic , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Breast Neoplasms/pathology , Capecitabine/adverse effects , Cyclophosphamide/adverse effects , Disease Progression , Disease-Free Survival , Female , Humans , Kaplan-Meier Estimate , Middle Aged , Multivariate Analysis , Neoplasm Metastasis , Proportional Hazards Models , Time Factors , Treatment Outcome , Vinblastine/administration & dosage , Vinblastine/adverse effects , VinorelbineABSTRACT
BACKGROUND: Letrozole withdrawal for 3 months might permit estrogenic stimulation in residual resistant breast cancer disease susceptible to letrozole reintroduction. We investigated the impact of a 3-month letrozole-free interval on serum estradiol levels in patients with early stage breast cancer. PATIENTS AND METHODS: Postmenopausal women with estrogen receptor- and/or progesterone receptor-positive (> 10% of immunoreactive cells), node-negative early breast cancer were eligible. Patients received letrozole for 5 years with a 3-month treatment-free interval after the first year of therapy. The primary end point was to evaluate the increase in serum estradiol levels after a 3-month treatment-free interval. The secondary end points were the evaluations of other biologic markers (eg, follicle-stimulating hormone, luteinizing hormone, cholesterol, high-density lipoprotein, triglycerides, osteocalcin). RESULTS: From November 2007 to February 2012, 130 evaluable patients were enrolled. The median age was 61 years. Mean values of estradiol levels at time of discontinuation were 5.6 pg/mL (standard deviation 1.7). Estradiol levels increased after a 3-month treatment-free interval by a mean of 3.3 pg/mL (66%; P < .0001). Follicle-stimulating hormone and luteinizing hormone levels decreased from baseline by a mean of 7.5 mU/mL (P < .0001), and 1.4 mU/mL (P = .0062), respectively. Triglycerides decreased from baseline by a mean of 8.6 mg/dL (P = .036), and osteocalcin increased by a mean of 2.8 ng/mL (P = .013). CONCLUSION: Intermittent letrozole significantly affects estradiol levels.
Subject(s)
Antineoplastic Agents, Hormonal/administration & dosage , Antineoplastic Agents/administration & dosage , Breast Neoplasms/drug therapy , Nitriles/administration & dosage , Postmenopause , Triazoles/administration & dosage , Aged , Biomarkers, Tumor/metabolism , Breast Neoplasms/metabolism , Chemotherapy, Adjuvant/methods , Female , Humans , Letrozole , Middle Aged , Receptors, Estrogen/metabolismABSTRACT
Effective treatment options for patients with metastatic breast cancer resistant to anthracyclines and taxanes are limited. Moreover, many chemotherapeutic agents need to be interrupted due to toxicity. Here we report an extremely long duration of chemotherapy with eribulin (11 courses) in a taxane-pretreated metastatic breast cancer patient. Therapy was well tolerated with no worsening of pre-existing neuropathy, achieving excellent outcomes and a good quality of life. This report adds to the pool of knowledge regarding the use of this important new metastatic breast cancer chemotherapeutic agent.
Subject(s)
Antineoplastic Agents/therapeutic use , Breast Neoplasms/drug therapy , Breast Neoplasms/pathology , Furans/therapeutic use , Ketones/therapeutic use , Adult , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Breast Neoplasms/diagnosis , Bridged-Ring Compounds/administration & dosage , Disease Progression , Female , Humans , Neoplasm Metastasis , Retreatment , Taxoids/administration & dosage , Treatment OutcomeABSTRACT
BACKGROUND: The aggressive biological behavior and the lack of target therapy prompts the search for new therapeutic approaches for triple-negative breast cancers. PATIENTS AND METHODS: We evaluated the efficacy in terms of Ki-67 variation and clinical response but also the toxicity of a neoadjuvant regimen based on metronomic principles including ECF (epidoxorubicin with cisplatin on day 1 with low-dose 5-fluorouracil in continuous infusion every 21 days for 4 courses) followed by paclitaxel (90 mg/m(2)) on day 1, 8, and 15 every 28 days for 3 courses in combination with metronomic oral cyclophosphamide 50 mg/d for 12 weeks in patients with HER2-negative breast cancer (T2-T4a-d, N0-3, M0) with estrogen receptor and progesterone receptor < 10%. RESULTS: We enrolled 34 patients from June 2009 to May 2013. All were considered evaluable on an intention-to treat basis. The mean difference between the percentage of Ki-67 positive cells evaluated in surgical resection specimens and in pretreatment tumor core biopsy was 41% (95% confidence interval [CI], 30-51; P < .0001) for the entire population, and 22% (95% CI, 7-38; P = .0097) in patients who did not achieve pathological complete response (pCR). Responses to the treatment were obtained in 31 patients [91%] of the patients, and 19 patients (56%; 95% CI, 35-70) had a pCR. Stable disease was observed in 3 patients and none had progressive disease. Grade ≥ 3 hematologic adverse events included leukopenia in 9% (3 of 34), neutropenia in 38% (13 of 34), and anemia in 3% (1 of 34) of patients. Nonhematologic Grade ≥ 3 toxicities included only stomatitis in 1 patient. CONCLUSION: A neoadjuvant program with an ECF regimen followed by weekly paclitaxel with metronomic cyclophosphamide proved to be very effective, with high pCR rates, reduction of Ki-67, and it was associated with a low toxicity profile.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Chemotherapy, Adjuvant/methods , Neoadjuvant Therapy/methods , Triple Negative Breast Neoplasms/drug therapy , Adult , Cisplatin/administration & dosage , Cisplatin/adverse effects , Cyclophosphamide/administration & dosage , Cyclophosphamide/adverse effects , Epirubicin/administration & dosage , Epirubicin/adverse effects , Female , Fluorouracil/administration & dosage , Fluorouracil/adverse effects , Humans , Middle Aged , Paclitaxel/administration & dosage , Paclitaxel/adverse effectsABSTRACT
BACKGROUND: Breast cancer occurs rarely in men, accounting for approximately 1% of all breast carcinomas. Data on prognosis principally derive from retrospective studies and from extrapolation of female breast cancer series. PATIENTS AND METHODS: A total of 99 men with invasive breast cancer were matched with 198 women with breast cancer who had surgery at the same institution from 1999 to 2010. Matching variables were year of surgery, age, primary tumor size, nodal involvement, hormone receptor status, status of HER2 (human epidermal growth factor receptor 2 [ERBB2]), Ki-67, and grade. Median follow-up was 8.6 years. RESULTS: Disease-free survival (DFS) was significantly poorer in the men (10-year DFS, 51.7% vs. 66.5%; hazard ratio [HR], 1.79; 95% CI, 1.19-2.68; P = .004). Similar results were observed for overall survival (OS) (10-year OS, 70.7% vs. 84.2%; HR, 1.79; 95% CI, 1.01-3.15; P = .043). The cumulative incidence of death for causes not related to the primary breast cancer was significantly higher for men than for women (HR, 2.87; 95% CI, 1.58-5.22; P = .001), whereas the breast cancer-specific survival (BCSS) was similar between the 2 groups (10-year BCSS, 81.5% vs. 88%; HR, 1.27; 95% CI, 0.62-2.59; P = .517). CONCLUSION: This comparative series found that men with breast cancer had a poorer DFS and OS when compared with women. The men also had a higher risk of contralateral tumors and second primaries. Appropriate counseling, surveillance, and prevention are recommended to improve survival for these individuals.
Subject(s)
Breast Neoplasms, Male/mortality , Breast Neoplasms, Male/pathology , Adult , Aged , Antineoplastic Agents/therapeutic use , Biomarkers, Tumor/analysis , Breast Neoplasms, Male/therapy , Combined Modality Therapy , Disease-Free Survival , Female , Humans , Kaplan-Meier Estimate , Male , Mastectomy , Middle Aged , Neoplasm Invasiveness , Radiotherapy , Treatment OutcomeABSTRACT
BACKGROUND: The prognostic implications of internal mammary (IM) and supraclavicular (SC) node involvement in locally advanced breast cancer is still unclear. PATIENTS AND METHODS: We evaluated 107 patients with IM (n = 65) or SC (n = 42) node involvement who underwent operation at the European Institute of Oncology between 1997 and 2009 to assess their prognostic features. We subsequently analyzed matched cohorts, using the 107 patients as cases and another group of patients as a control cohort, to evaluate prognostic differences between patients with and those without IM or SC node involvement. RESULTS: Five-year disease-free survival (DFS) was 84% in IM vs. 38.8% in SC node involvement (P < .0001), and 5-year overall survival (OS) was 96.9% in IM node vs. 57.1% in SC node involvement (P < .0001). No difference in outcome was found between patients with and controls without IM node involvement. Conversely, a statistically significant difference in DFS and locoregional recurrence was observed in patients with SC node involvement compared with controls without SC node involvement. CONCLUSION: SC node involvement correlated with a significantly poorer outcome in patients with locally advanced breast cancer. Adequate staging, including biopsy of suspicious locoregional ipsilateral lymph nodes, is mandatory in these patients. Patients with IM or SC node involvement should be treated with curative intent using combined-modality treatments.
Subject(s)
Breast Neoplasms/pathology , Adult , Aged , Breast Neoplasms/mortality , Breast Neoplasms/therapy , Disease-Free Survival , Female , Humans , Lymphatic Metastasis , Middle Aged , Neoplasm StagingABSTRACT
BACKGROUND: Conflicting data are available in the literature on the outcome of invasive apocrine carcinoma (IAC), possibly related to a heterogeneous classification of these tumors. PATIENTS AND METHODS: A series of 6899 consecutive patients with invasive ductal carcinoma (IDC) not otherwise specified and 72 patients with immunohistochemically defined IAC who received surgery at the European Institute of Oncology between 1997 and 2005 were included. We then explored patterns of recurrence of IAC according to 2 immunohistochemically defined tumor subtypes: pure apocrine carcinoma (estrogen [ER] and progesterone [PgR] receptor negative, and AR positive) and apocrine-like carcinoma (ER or PgR positive and AR negative). RESULTS: The diagnosis of pure apocrine carcinoma was correlated with a worse outcome in terms of DFS (hazard ratio [HR] 1.7; 95% confidence interval [CI], 1.01-2.86; P = .0010) if compared with IDC, whereas IDC and apocrine-like breast cancers showed a similar outcome in terms of DFS and overall survival. Patients with pure apocrine carcinoma had an increased risk in contralateral breast cancer (HR, 4.12; 95% CI, 1.22-14; P = .02). CONCLUSION: Pure apocrine carcinoma represents a distinct subtype of breast cancer with a significantly worse DFS as compared with IDC. AR determination might have an important prognostic implication in IAC. Moreover, AR-targeted therapy should be further explored within these tumors.
Subject(s)
Apocrine Glands/pathology , Biomarkers, Tumor/metabolism , Breast Neoplasms/classification , Carcinoma, Ductal, Breast/classification , Carcinoma, Lobular/classification , Neoplasm Recurrence, Local/pathology , Adult , Aged , Aged, 80 and over , Apocrine Glands/surgery , Breast Neoplasms/metabolism , Breast Neoplasms/mortality , Breast Neoplasms/pathology , Carcinoma, Ductal, Breast/metabolism , Carcinoma, Ductal, Breast/mortality , Carcinoma, Ductal, Breast/pathology , Carcinoma, Lobular/metabolism , Carcinoma, Lobular/mortality , Carcinoma, Lobular/pathology , Female , Follow-Up Studies , Humans , Immunoenzyme Techniques , Middle Aged , Neoplasm Recurrence, Local/metabolism , Neoplasm Recurrence, Local/mortality , Neoplasm Staging , Prognosis , Receptor, ErbB-2/metabolism , Receptors, Androgen/metabolism , Receptors, Estrogen/metabolism , Receptors, Progesterone/metabolism , Survival Rate , Young AdultABSTRACT
BACKGROUND: This study assesses outcome in terms of disease-free survival (DFS) and overall survival (OS) of special types of triple-negative breast cancer (TNBC). PATIENTS AND METHODS: We identified 8801 women with first primary nonmetastatic breast cancer operated on at the European Institute of Oncology between 1997 and 2005. Of these patients, 781 consecutive patients with immunohistochemically defined TNBC were selected for the analyses. We explored patterns of recurrence by histologic type. Median follow-up was 5.7 years (range 0-13 years). RESULTS: The 5-year DFS was 77% for TNBC, 68% for human epidermal growth factor receptor 2 (HER2)-positive breast cancer, and 84% and 95% for luminal B and luminal A breast cancer, respectively. From 781 TNBC subtypes, 693 cases (89%) were classified as ductal not otherwise specified (NOS) (invasive ductal carcinoma [IDC]), 29 were classified as apocrine (3.7%), 18 (2.3%) were classified as lobular, 10 (1.2%) were classified as adenoid cystic, and 10 (1.2%) were classified as metaplastic. Five-year DFS and OS were 77% and 84% for patients with ductal carcinoma, 56% and 89% for patients with metaplastic carcinoma, and both 5-year DFS and OS were 100% for patients with adenoid cystic and medullary carcinomas, respectively. CONCLUSION: Distinct prognostic implications may derive from the specific histotype of TNBC. The identification of these special types has a significant clinical utility and should be considered in therapeutic algorithms.
Subject(s)
Biomarkers, Tumor/metabolism , Breast Neoplasms/mortality , Carcinoma, Ductal, Breast/mortality , Carcinoma, Lobular/mortality , Receptor, ErbB-2/metabolism , Receptors, Estrogen/metabolism , Receptors, Progesterone/metabolism , Breast Neoplasms/metabolism , Breast Neoplasms/therapy , Carcinoma, Ductal, Breast/metabolism , Carcinoma, Ductal, Breast/therapy , Carcinoma, Lobular/metabolism , Carcinoma, Lobular/therapy , Combined Modality Therapy , Female , Follow-Up Studies , Humans , Immunoenzyme Techniques , Lymphatic Metastasis , Neoplasm Staging , Prognosis , Survival RateABSTRACT
Invasive lobular carcinoma (ILC) is the most common "special type" of breast cancer. Although conflicting literature data are available on the outcome of ILC, recently reported data indicate that ILC carries a poorer prognosis if compared to invasive ductal carcinomas. We evaluated clinical and biological features of 981 consecutive patients with pT1-3, pN1-3 M0 ILC. Median follow-up was 7.4 years for survival. A total of 541 patients were classified as classic (55.8%), 146 alveolar (14.9%), 145 mixed non-classic (14.8%), 104 solid (10.6%), and 38 trabecular (3.9%). A statistically significant difference in the outcome was observed at multivariate analysis for patients with solid (HR 2.44, 95% CI 1.39-4.29 for OS; HR 1.92, 95% CI 1.29-2.88 for DFS) and mixed non-classic (HR 1.99, 95% CI 1.12-3.53 for OS) versus patients with classical ILC. A statistically significant difference in the risk of distant metastases was observed at multivariate analysis for patients with Luminal B (HR 2.56, 95% CI 1.38-4.76), HER2 positive (HR 7.80, 95% CI 1.55-39.3), and triple negative (HR 7.61, 95% CI 2.63-22.1) subtypes versus patients with Luminal A ILC. Age ≥70 years, tumor size and degree of nodal involvement were additional independent predictors of reduced overall survival. The outcome of ILC significantly correlated with histological and immunohistochemically defined molecular subtypes. New tailored strategies should be explored in these subgroups of patients with poor outcome.
Subject(s)
Breast Neoplasms/mortality , Breast Neoplasms/pathology , Carcinoma, Lobular/mortality , Carcinoma, Lobular/pathology , Adult , Aged , Aged, 80 and over , Breast Neoplasms/classification , Breast Neoplasms/therapy , Carcinoma, Lobular/classification , Carcinoma, Lobular/therapy , Female , Follow-Up Studies , Humans , Middle Aged , Neoplasm Staging , Prognosis , Retrospective Studies , Survival Analysis , Young AdultABSTRACT
Patients with large ER positive tumors candidate to preoperative chemotherapy may also benefit from a concurrent endocrine intervention, but this issue has been scarcely investigated due to concerns arising from unfavorable results emerged from an adjuvant trial of concurrent tamoxifen and chemotherapy. We retrospectively investigated the activity of letrozole plus GnRH analogue (GnRH-a) administered concurrently with preoperative chemotherapy and as adjuvant treatment in premenopausal women with locally advanced ER positive breast cancer consecutively admitted at the European Institute of Oncology. Results were compared with those of a non-randomized unmatched control group of premenopausal women with locally advanced ER positive breast cancer receiving preoperative chemotherapy, followed by tamoxifen and GnRH-a after surgery. Primary endpoints were pathological complete response (pCR) rate, decrease of Ki67 and disease free survival (DFS). One-hundred and nineteen women constituted the study group, while 95 patients served as controls. The pCR rate was 5.0 vs 1.1% in the study and control group, respectively. A statistically significant greater suppression of Ki67 was observed in patients receiving chemoendocrine therapy as compared with controls (P = 0.003). At a median follow up of 59 months, 26 events occurred in the chemoendocrine group and 48 in the control group. Five-year DFS was 78 vs 41% in the study and in the control group, respectively [adjusted HR 0.46, 95% CI 0.27-0.79, P = 0.0047]. The concurrent administration of letrozole and GnRH-a with preoperative chemotherapy was highly effective in premenopausal women with large ER positive breast cancer in terms of decreased proliferation and of improved DFS. Randomized studies are warranted to establish the role of the addition of endocrine therapy to chemotherapy as standard preoperative approach for ER positive locally advanced breast cancer as well as of letrozole in combination with GnRH-a for the treatment of premenopauasal women with early breast cancer.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Breast Neoplasms/therapy , Carcinoma, Ductal, Breast/therapy , Carcinoma, Lobular/therapy , Receptors, Estrogen/metabolism , Adult , Breast Neoplasms/metabolism , Breast Neoplasms/mortality , Carcinoma, Ductal, Breast/metabolism , Carcinoma, Ductal, Breast/mortality , Carcinoma, Lobular/metabolism , Carcinoma, Lobular/mortality , Chemotherapy, Adjuvant , Disease-Free Survival , Estradiol/metabolism , Female , Gonadotropin-Releasing Hormone/administration & dosage , Gonadotropin-Releasing Hormone/analogs & derivatives , Humans , Ki-67 Antigen/metabolism , Letrozole , Middle Aged , Neoadjuvant Therapy , Nitriles/administration & dosage , Premenopause , Receptor, ErbB-2/metabolism , Receptors, Progesterone/metabolism , Retrospective Studies , Treatment Outcome , Triazoles/administration & dosageABSTRACT
PURPOSE: To explore the activity of pegylated liposomal doxorubicin (PLD) as neoadjuvant therapy of breast cancer. METHODS: The combination of PLD with cisplatin and infusional fluorouracil (CCF) for 8 courses was investigated in patients with primary or recurrent T2-T4a-d N0-3 M0 breast cancer. Patients with ER and/or PgR ≥10% tumors also received letrozole (±triptorelin). RESULTS: Forty patients entered the study. Four patients had recurrent tumors and 13 had cT4d tumors. Overall, clinical response rate was 77.5% whereas a pathological complete response (pCR) was obtained in 3 patients (7.7%), 4 when considering bilateral tumors. Noticeably 3 pCR were observed among the 10 patients with T4d ER positive tumors (33%). Eleven patients discontinued treatment before completion of the 8 planned courses. CONCLUSIONS: Our results indicated that CCF yielded an appreciable rate of clinical responses in a series of very locally advanced tumors and an unusually high rate of pCR in T4d ER positive tumors, suggesting an enhanced cutaneous activity of PLD.