OBJECTIVE: Adipocytes secrete a series of acute phase proteins including serum amyloid A (SAA); the link with metabolic status is unknown. We studied the variations of expression of the SAA gene in ...adipose and liver tissues and of SAA serum levels, as well as their relationships with metabolic features during weight loss. RESEARCH METHODS AND PROCEDURES: Plasmatic variations of SAA, inflammatory markers (high sensitivity C-reactive protein, interleukin-6, fibrinogen, and orosomucoid), and adipokines (adiponectin, leptin) were studied in 60 morbidly obese patients before and after gastric surgery. For 10 subjects, SAA mRNA expression was measured at baseline in subcutaneous white adipose tissue (scWAT) and visceral white adipose tissue (vWAT) and in the liver. The evolution of SAA mRNA expression was also studied after surgery in scWAT. RESULTS: SAA serum concentration displayed a significant reduction 3 months after surgery and remained stable beyond 6 months. mRNA expression of inducible SAA isoforms (SAA 1 and 2) in scWAT was higher than in vWAT (p = 0.01) and the liver (p < 0.01) and correlated significantly with BMI, SAA, and high sensitivity C-reactive protein serum concentrations but not with metabolic markers (glucose, insulin, lipid parameters, adiponectin). SAA serum level and its variation during weight loss significantly correlated with adiposity markers (BMI and adipocyte volume, p < 0.01) and inflammatory markers but not with variations of metabolic parameters. The variations of SAA expression in scWAT after surgery correlated with changes in BMI and SAA protein serum levels (p < 0.05). DISCUSSION: SAA can be considered as a marker of adiposity-induced low-grade inflammation but not of the metabolic status of obese subjects.
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.
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/m
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.
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.
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.
Inflammatory breast cancer is a rare and highly aggressive disease. We investigated in a phase II study a neoadjuvant regimen with chemotherapy and an antiangiogenic strategy. The pathologic complete ...remission (pCR) rate was 29% and was significantly greater in patients with HER2+ tumors (57%). The achievement of a pCR was associated with longer disease-free and overall survival. The investigated regimen was effective and well tolerated. The antiangiogenic strategy warrants further studies in this setting.
Inflammatory breast cancer (IBC) is a rare and highly aggressive disease. A neoadjuvant regimen with chemotherapy and an antiangiogenic strategy was investigated.
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.
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.
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.
Background: The prognostic role of serum levels of molecular biomarkers during the perioperative period in patients with early
breast cancer is not clear. Patients and Methods: Serum VEGF and ...extracellular domains (ECD) of EGFR and HER2 were prospectively
determined in 119 consecutive patients with early breast cancer on the day before and after surgery. Results: After a median
follow-up of 93 months, the preoperative value and the absolute change from pre- to postoperative serum levels of VEGF and
HER2 ECD did not predict disease-free survival (DFS). A decrease after surgery of EGFR ECD correlated with a statistically
significant lower DFS; each 1 ng/ml decrease in EGFR ECD serum level was associated with an increase of event risk of 15%
on multivariable analysis (hazard ratio 1.15 95% confidence interval 1.04.-1.28, p=0.006). Conclusion: The perioperative absolute
change of EGFR ECD significantly correlated with disease outcome of patients with early breast cancer. No correlation was
found between preoperative and perioperative absolute change of serum VEGF and HER2 ECD.
Micro-Abstract Postmenopausal women with estrogen receptor– and/or progesterone receptor–positive, node-negative early breast cancer was eligible for this study. All patients received letrozole for 5 ...years with a 3-month treatment-free interval after the first year. Estradiol levels increased after a 3-month treatment-free interval by a mean of 3.3 pg/mL ( P < .0001). Intermittent letrozole significantly affects estradiol levels.
Abstract Background Pegylated liposomal doxorubicin (PLD) was shown as active but less toxic compared to doxorubicin in advanced breast cancer. Given its low cardiotoxicity, the combination of PLD ...and trastuzumab appears most attractive in the treatment of human epidermal factor receptor 2 (HER2)-positive breast cancer. Patients and Methods: We investigated the activity of 8 courses of PLD in combination with cisplatin and infusional 5-fluorouracil (CCF) plus 3-week trastuzumab in patients with primary or recurrent cT2-T4 a-d, N0-3, M0 any estrogen receptor (ER), HER2-positive breast cancer. Patients with ER and/or progesterone receptor (PgR) ≥ 10% tumors received also letrozole (plus triptorelin if premenopausal). The principal endpoint was clinical response rate; secondary endpoints were the pathologic complete response rate (pCR) and the cardiac safety of the combination. Results: Thirty-two patients were enrolled in the study and all are evaluable for response and toxicity. Fifteen patients (47%) had ER-positive tumors, 15 patients and 2 patients had ER absent and ER poor tumors, respectively. Thirteen patients (41%) had inflammatory breast cancer (IBC) and 84% of patients had clinically positive nodes. A clinical response rate of 94% (95% CI, 79%-99%) and a pCR rate of 41% (95% CI, 24%-59%) were observed. Fifty-four percent of patients with IBC obtained a pCR. Eleven patients discontinued treatment before completing 8 courses as planned. No patient developed relevant cardiac toxicity. Conclusion: In this series of very locally advanced breast cancer, the combination of CCF and trastuzumab was very active obtaining an impressive rate of pCR, particularly in IBC, which merits further investigation in larger series.
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