33 research outputs found
Rare Case of Male Breast Cancer and Axillary Lymphoma in the Same Patient: An Unique Case Report
Breast cancer in men is uncommon, and even more rare is the simultaneous presentation of two different malignancies. A 39-year-old man was diagnosed with both breast cancer and axillary lymphoma. Familiar history revealed that his mother died because of breast cancer. The patient underwent fine needle aspiration leading to the diagnosis of malignant lesion. Modified radical mastectomy was performed. Histology revealed an infiltrating ductal carcinoma 2.8 cm wide, grade 2, with vascular and lymphatic invasion. Surprisingly, one of the second level nodes was confirmed as a high-grade large B cell non-Hodgkin's lymphoma. No family inheritance or gene mutations (BRCA 1 and 2) were found. The patient underwent local radiotherapy, followed by 6 chemotherapy courses (RCHOP) and treatment with tamoxifen 20 mg/daily. To our knowledge, this is the first case reported in literature of male breast cancer and axillary lymphoma simultaneously confirmed in the same patient
Rare Case of Male Breast Cancer and Axillary Lymphoma in the Same Patient: An Unique Case Report
Breast cancer in men is uncommon, and even more rare is the simultaneous presentation of two different malignancies. A 39-year-old man was diagnosed with both breast cancer and axillary lymphoma. Familiar history revealed that his mother died because of breast cancer. The patient underwent fine needle aspiration leading to the diagnosis of malignant lesion. Modified radical mastectomy was performed. Histology revealed an infiltrating ductal carcinoma 2.8 cm wide, grade 2, with vascular and lymphatic invasion. Surprisingly, one of the second level nodes was confirmed as a high-grade large B cell non-Hodgkin's lymphoma. No family inheritance or gene mutations (BRCA 1 and 2) were found. The patient underwent local radiotherapy, followed by 6 chemotherapy courses (RCHOP) and treatment with tamoxifen 20 mg/daily. To our knowledge, this is the first case reported in literature of male breast cancer and axillary lymphoma simultaneously confirmed in the same patient
PIK3CA MUTATIONS IN HER2-POSITIVE BREAST CANCER PATIENTS ENROLLED IN THE ADJUVANT RANDOMIZED SHORT-HER STUDY.
Different semantic and affective meaning of the words associated to physical and social pain in cancer patients on early palliative/supportive care and in healthy, pain-free individuals
Homologous recombination deficiency, RB-loss gene signatures, intrinsic subtype and response to neoadjuvant treatment in HR+/HER2- early breast cancer: a correlative analysis of two phase II trials
Background: Hormone-receptor (HR)+/HER2- breast cancer (BC) is a biologically heterogeneous disease. Homologous recombination deficiency (HRD) and BRCA mutations have been previously reported to be associated with worse outcomes in HR+/HER2- metastatic BC patients receiving CDK4/6 inhibitors and endocrine therapy. Here, we assess the relation between HRD and RB-loss signatures, intrinsic subtyping, the PAM50-based chemo-endocrine score, and response to chemotherapy-based therapy and endocrine treatment in HR+/HER2- early BC. Methods: GIADA is a multicentric neoadjuvant phase II trial that treated premenopausal patients with Luminal B (LumB)-like BC (HR-positive, HER2-negative, with Ki67>20% and/or histologic Grade 3) with a combination of chemotherapy, immunotherapy and endocrine treatment. Expression of 758 genes on baseline tumor samples from all 43 patients was quantified by nCounter platform. The LETLOB phase II trial randomized postmenopausal women with clinical stage II-IIIA HR+/HER2- BC to neoadjuvant letrozole + lapatinib or letrozole + placebo for 6 months (Guarneri, JCO 2014). Gene-expression data (Affymetrix platform) from pre-treatment frozen core-biopsies was available from 66 out of 92 pts enrolled. Intrinsic subtype was assigned using a research-based PAM50 subtype predictor. A published HRD signature (Peng, Nat Commun 2014) and a signature of RB loss (RBsig), previously reported to potentially predict resistance to CDK4/6 inhibitors in HR+/HER2- BC (Malorni, Oncotarget 2016) were computed. The PAM50 based chemo-endocrine score (CES) was calculated using published definition (Prat, CCR 2017). Higher values of CES indicate increased endocrine sensitivity, while lower values indicate chemosensitivity. Association between genomic signatures was assessed through Pearson’s correlation coefficient. Association of genomic signatures with pCR was assessed through logistic regression and association with PEPI scores was assessed through Kruskal-Wallis test. Results: HRD signature levels were significantly higher in non-luminal (Basal-like and HER2-enriched) tumors as compared to Luminal (A or B) tumors (p>0.001 in the GIADA trial, p=0.021 in the LETLOB trial). Moreover, higher levels of HRD signature were associated with higher levels of RB-loss signature (Pearson correlation 0.355, p=0.020 in the GIADA trial; Pearson correlation 0.942, p< 0.001 in the LETLOB trial), higher levels of Basal-like signature (Pearson correlation 0.502, p< 0.001 in the GIADA trial; Pearson correlation 0.373, p=0.002 in the LETLOB trial) and lower levels of CES (Pearson correlation -0.422, p=0.005 in the GIADA trial; Pearson correlation -0.763, p< 0.001 in the LETLOB trial), indicative of higher chemosensitivity. In the GIADA trial, higher levels of HRD signature (p=0.018) and RBloss signature (p=0.073) and lower levels of CES (p=0.007) were associated with higher pCR rates after chemo, endocrine and immunotherapy. In the LETLOB trial, lower levels of HRD signature (p=0.068) and RBloss signature (p=0.042) and higher levels of CES (p=0.050) were associated with higher sensitivity to endocrine treatment (lower PEPI scores, 0 vs 1-3 vs 4 or more, after neoadjuvant letrozole). Conclusions: In HR+/HER2- early BC, HRD gene signatures, RB-loss gene signatures and non-luminal (especially Basal-like) intrinsic subtyping are associated with each other and associated with higher sensitivity to chemotherapy-based therapy and lower sensitivity to endocrine treatment. These observations might help correctly tailor systemic therapy, including biologic agents, in patients with HR+/HER2- early and advanced BC
PIK3CA Mutation in the ShortHER Randomized Adjuvant Trial for Patients with Early HER2\ufe Breast Cancer: Association with Prognosis and Integration with PAM50 Subtype.
Purpose: We explored the prognostic effect of PIK3CA mutation
in HER2\ufe patients enrolled in the ShortHER trial.
Patients and Methods: The ShortHER trial randomized 1,253
patients with HER2\ufe breast cancer to 9 weeks or 1 year of adjuvant
trastuzumab combined with chemotherapy. PIK3CA hotspot mutations in exon 9 and 20 were analyzed by pyrosequencing. Expression
of 60 genes, including PAM50 genes was measured using the
nCounter platform.
Results: A mutation of the PIK3CA gene was detected in
21.7% of the 803 genotyped tumors. At a median follow-up of
7.7 years, 5-year disease-free survival (DFS) rates were 90.6%
for PIK3CA mutated and 86.2% for PIK3CA wild-type tumors
[HR, 0.84; 95% confidence interval (CI), 0.56\u20131.27; P \ubc 0.417].
PIK3CA mutation showed a favorable prognostic impact in
the PAM50 HER2-enriched subtype (n \ubc 232): 5-year DFS
91.8% versus 76.1% (log-rank P \ubc 0.049; HR, 0.46; 95% CI,
0.21\u20131.02). HER2-enriched/PIK3CA mutated versus wild-type
tumors showed numerically higher tumor-infiltrating lymphocytes (TIL) and significant upregulation of immune-related
genes (including CD8A, CD274, PDCD1, and MYBL2, a proliferation gene involved in immune processes). High TILs as well
as the upregulation of PDCD1 and MYBL2 were associated with
a significant DFS improvement within the HER2-enriched subtype (HR, 0.82; 95% CI, 0.68\u20130.99; P \ubc 0.039 for 10% TILs
increment; HR, 0.81; 95% CI, 0.65\u20130.99; P \ubc 0.049 for PDCD1
expression; HR, 0.72; 95% CI, 0.53\u20130.99; P \ubc 0.042 for MYBL2
expression).
Conclusions: PIK3CA mutation showed no prognostic impact in
the ShortHER trial. Within the HER2-enriched molecular subtype,
patients with PIK3CA mutated tumors showed better DFS versus
PIK3CA wild-type, which may be partly explained by upregulation
of immune-related genes
Trastuzumab-lapatinib as neoadjuvant therapy for HER2-positive early breast cancer: Survival analyses of the CHER-Lob trial.
AIM: The Cher-LOB randomised phase II study showed that the combination of lapatinib-trastuzumab plus chemotherapy increases pathologic complete response (pCR) rate compared with chemotherapy plus either trastuzumab or lapatinib. Here, we report the post hoc survival analysis as per treatment arm, pCR and biomarkers. METHODS: The Cher-LOB study randomised 121 patients with human epidermal growth factor receptor 2-positive, stage II-IIIA breast cancer. A specific protocol to collect recurrence-free survival (RFS) and overall survival (OS) data was designed. Tumour-infiltrating lymphocytes (TILs) and PAM50-intrinsic subtyping were evaluated at baseline. RESULTS: At 9-year median follow-up, a trend towards RFS improvement with lapatinib-trastuzumab over trastuzumab was observed (hazard ratio [HR] 0.44, 95% confidence interval [CI] 0.18-1.05). Combining treatment arms, pCR was significantly associated with both RFS (HR 0.12, 95% CI 0.03-0.49) and OS (HR 0.12, 95% CI 0.03-0.49). TILs were significantly associated with RFS (HR = 0.978 for each 1% increment). Luminal-A subtype was a significant and independent predictor of improved RFS as compared with other PAM50-based intrinsic subtypes at the multivariate analysis including the most relevant clinicopathologic variables (HR 0.29, 95% CI 0.09-0.94, p = 0.040). CONCLUSIONS: Cher-LOB trial survival analysis confirmed the prognostic role of pCR and TILs and showed a signal for a better outcome with lapatinib-trastuzumab over trastuzumab. TRIAL REGISTRATION: NCT00429299
Tumor infiltrating lymphocytes and correlation with pCR in ther CHERLOB study
Body: Background: Over one-third of patients (pts) with HER2-positive (+) advanced breast cancer (BC) develop brain
metastases (BM), which often leads to short survival. Afatinib (A), an irreversible ErbB family blocker, demonstrated activity in pts
with heavily pretreated, HER2+ metastatic BC (MBC) progressing after trastuzumab (T) therapy, with partial responses (PR) in
10% and clinical benefit in 46% of pts (Lin 2012a). We evaluated the activity of A alone or in combination with vinorelbine (V),
versus investigator’s choice of therapy for MBC (IC), in pts with HER2+ BC with BM after prior T and/or lapatinib (L) therapy.
Methods: Eligible pts had at least one measurable and progressive lesion in the central nervous system (CNS; ³10 mm on
magnetic resonance imaging) after prior systemic and/or radiation therapy. Pts were randomized to receive A (40 mg/day oral),
AV (40 mg/day oral + 25 mg/m2/week i.v.) or IC in 3-week cycles. Stratification factors were: ECOG performance status (PS, 0–1
vs 2), number of BM (£3 vs >3) and prior exposure to L (yes/no). The primary endpoint was pt benefit at 12 weeks (i.e. absence
of CNS and extra-CNS disease progression per RECIST 1.1, and no tumor-related worsening of neurological signs/symptoms or
increase in steroid dosage). Secondary endpoints included progression-free survival (PFS), overall survival (OS), objective
response rate (ORR) in CNS/extra-CNS lesions, and safety.
Results: 121 pts were randomized (2 were not treated): median age, 53 years; ECOG PS 0–1, 83%; >3 BM, 59%; prior L therapy,
78.5%. The IC treatment consisted of: T+ chemotherapy (CT) (22 pts); T+L+CT (3 pts); L+CT (10 pts); L alone (1 pt); or CT alone
(6 pts). In the treated set (n=119), the most frequent treatment-related adverse events (AEs) in the A and AV arms were diarrhea (90%
and 84%) and rash (38% and 54%); neutropenia (51%) was also common in the AV arm. Diarrhea (33%), neutropenia (21%) and
asthenia (21%) were the most frequent related AEs in the IC arm. Grade (G) 3/4 treatment-related AEs were observed in 50%/3% (A), 57%/24% (AV; G4 AEs were mainly neutropenias) and 14%/7% (IC) of pts; there were no treatment-related G5 events.
Conclusions: Approximately one third of pts with HER2+ MBC benefited from the assigned treatments and two thirds had CNS
lesions controlled per RECIST in each group. Objective response in CNS was infrequent (0 to 14%) with all treatments. Overall,
AEs were manageable in this heavily pretreated pt population
Immune microenvironment and intrinsic subtyping in hormone receptor-positive/HER2-negative breast cancer
Little is known regarding the interaction between immune microenvironment and tumor biology in hormone receptor (HR)+/HER2- breast cancer (BC). We here assess pretreatment gene-expression data from 66 HR+/HER2- early BCs from the LETLOB trial and show that non-luminal tumors (HER2-enriched, Basal-like) present higher tumor-infiltrating lymphocyte levels than luminal tumors. Moreover, significant differences in immune infiltrate composition, assessed by CIBERSORT, were observed: non-luminal tumors showed a more proinflammatory antitumor immune infiltrate composition than luminal ones
Preoperative Carboplatin\u2013Paclitaxel\u2013Bevacizumab in Triple-Negative Breast Cancer: Final Results of the Phase II Ca.Pa.Be Study
none9noPURPOSE:
The phase II Ca.Pa.Be trial evaluated preoperative carboplatin-paclitaxel in combination with bevacizumab in triple-negative breast cancer patients with previously untreated stage II-III disease. The primary aim was the assessment of the rate of pathologic complete response (pCR). Secondary aims included safety, breast-conserving surgery rate, and early response assessment with dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI).
METHODS:
Patients with hormone receptor-negative, HER-2-negative stage II-III breast cancer were eligible. Treatment included paclitaxel 80 mg/mq + carboplatin area under the curve (AUC) 2 on days 1, 8, and 15, combined with bevacizumab 10 mg/kg on days 1 and 15 each 28 days, for 5 courses. At baseline, patients underwent breast DCE-MRI, followed by a single dose of bevacizumab 5 mg/kg (day -6). DCE-MRI was repeated before the initiation of chemotherapy.
RESULTS:
Forty-four patients were enrolled. Forty-three patients underwent surgery, and 22 (50 %) received breast-conserving surgery (conversion rate from mastectomy indication at baseline, 34.4 %). A pCR in breast and axillary lymph nodes occurred in 22 patients (50 %). Bevacizumab-associated adverse events (AEs) were mild: G1-2 hypertension and bleeding occurred in 6 (13.6 %) and 12 (27 %) patients, respectively. No G4 nonhematologic AEs were recorded. More frequent G3 AEs were liver function test abnormalities (6.8 %), and diarrhea and fatigue (4.5 % each). The only G3-4 hematologic toxicity was neutropenia (G3, 25 %; G4, 9 %). Early assessed DCE-MRI response parameters failed to predict pCR.
CONCLUSIONS:
The neoadjuvant anthracycline-free combination of weekly paclitaxel and carboplatin plus bevacizumab is active and safe in triple-negative breast cancer, and the rate of pCR is comparable to that observed with more intensive carboplatin- and bevacizumab-containing regimens. Further investigation is warranted.noneGuarneri V;Dieci MV;Bisagni G;Boni C;Cagossi K;Puglisi F;Pecchi A;Piacentini F;Conte PGuarneri, Valentina; Dieci, MARIA VITTORIA; Bisagni, G; Boni, C; Cagossi, K; Puglisi, F; Pecchi, A; Piacentini, F; Conte, Pierfranc