Pneumocystis jiroveci pneumonia (PCP) in patients receiving neoadjuvant and adjuvant anthracycline-based chemotherapy for breast cancer: incidence and risk factors

Abstract

Opportunistic infection with Pneumocystis jiroveci pneumonia (PCP) has not been recognized as a significant complication of early-stage breast cancer treatment. However, we have observed an increase in PCP incidence among patients receiving chemotherapy for early-stage breast cancer. Herein we identify risk factors for and calculate incidence of PCP in this population. We identified all cases of PCP at Dana-Farber Cancer Institute/Brigham and Women's Hospital (DFCI/BWH) from 1/1/2000 to 12/31/2013 in patients with stage I-III breast cancer treated with an adriamycin/cyclophosphamide (AC)-containing regimen. Nineteen cases of PCP in non-metastatic breast cancer patients were identified. All patients with PCP were diagnosed after receipt of either three or four cycles of AC chemotherapy on a dose-dense schedule. Patients who developed PCP were treated with median 16.4 mg prednisone equivalents/day as nausea prophylaxis for a median 64 days. The overall incidence of PCP among 2057 patients treated with neoadjuvant or adjuvant dose-dense AC for three or more cycles was 0.6 % (95 % confidence interval 0.3-1.0 %). No PCP was diagnosed in 1001 patients treated with non-dose-dense AC. There was one death from PCP. Women receiving dose-dense AC chemotherapy for early-stage breast cancer are at risk for PCP. Administering the same chemotherapy and corticosteroid dose over an 8-week versus 12-week non-dose-dense schedule appears to have created a novel infectious vulnerability. Replacing dexamethasone with alternative anti-emetics may mitigate this risk.

Prevalence and Etiology of Community-acquired Pneumonia in Immunocompromised Patients

“…Hematological cancer and chemotherapy were other leading immunocompromised factors. These findings are consistent with those in previous studies; patients recruited in observational studies include patients with solid or hematological cancer and those who underwent chemotherapy with associated neutropenia [15][16][17][18][19][20]22]. Dedicated guidelines and recommendations are available, especially on respiratory viruses, fungi, and P. jirovecii [23][24][25][26].…”

“…Randomized controlled trials (RCTs) and observational prospective studies are missing owing to the fact that, generally, studies assessing management strategies for pneumonia exclude immunocompromised patients or take into account only a single specific risk factor [12][13][14][15][16][17][18][19][20][21]. This lack of information about immunocompromise could lead to both underestimation of the real prevalence with a higher rate of treatment failure and to overestimation and overuse of wide-spectrum antibiotics.…”

“…Infections by P. jirovecii and NTM are frequently identified in patients with AIDS [35]. P. jirovecii is also frequent in other types of immunocompromise, such as solid or hematological cancer in patients who underwent chemotherapy [18,19,36]. Fungal infections (eg, Candida spp.…”

Pneumocystis jirovecii in a patient on dose‐dense chemotherapy for early breast cancer

“…Whilst it has been described in HIV-negative patients with advanced solid tumours, it is not a well-recognized complication of EBC treatment, with data largely confined to single case reports or small case series only. More recently, Waks et al identified 19 cases of PJP amongst a series of 2057 patients receiving the ddAC-containing regimen for EBC [9]. All 19 cases were diagnosed after at least three doses of AC chemotherapy on a dose-dense schedule, giving an overall incidence of 0.6% (95% confidence interval 0.3-1.0%).…”

<i>Pneumocystis jirovecii</i> Pneumonia in a Patient with Breast Cancer Receiving Neoadjuvant Dose-dense Chemotherapy

“…However, the use of corticosteroids in chemotherapy regimens has been consistently reported as a major risk factor (8). Recently, there have been isolated reports of PCP in patients on dose-dense AC chemotherapy for early breast cancer (9)(10)(11). In the dose-dense AC regimen, these agents are administered on an every-twoweeks schedule, while in the standard AC regimen, they are administered on an every-three-weeks schedule.…”