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 Table of Contents  
CASE REPORT
Year : 2022  |  Volume : 5  |  Issue : 1  |  Page : 21-24

Drug-Induced interstitial pneumonitis in a case of breast malignancy


Department of Pulmonary Medicine, Government Stanley Medical College, Chennai, Tamil Nadu, India

Date of Submission26-Mar-2022
Date of Decision24-Apr-2022
Date of Acceptance02-May-2022
Date of Web Publication12-Aug-2022

Correspondence Address:
Hemalatha Padmanathan
Assistant Professor of Pulmonary Medicine, Government Stanley Medical College, Chennai, Tamil Nadu
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/japt.japt_5_22

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  Abstract 


Drugs used in the treatment of diseases including malignancy are known to cause various lung injuries, including interstitial pneumonitis. With increasing incidence of malignancies and advent of newer and newer chemotherapy and immunological treatments, it is prudent on the part of the pulmonologist to identify such complications at the earliest so that appropriate treatment can be initiated and reduce morbidity and mortality due to such causes. Herewith is presented a case of a patient with invasive ductal carcinoma of the breast who developed interstitial pneumonitis after 2 weeks of treatment with docetaxel and trastuzumab and was managed successfully.

Keywords: Breast cancer, chemotherapy, docetaxel, interstitial, pneumonitis, trastuzumab


How to cite this article:
Padmanathan H, Murugesan H, Kumaran S, Selvam R, Pandian V, Viswanathan VK. Drug-Induced interstitial pneumonitis in a case of breast malignancy. J Assoc Pulmonologist Tamilnadu 2022;5:21-4

How to cite this URL:
Padmanathan H, Murugesan H, Kumaran S, Selvam R, Pandian V, Viswanathan VK. Drug-Induced interstitial pneumonitis in a case of breast malignancy. J Assoc Pulmonologist Tamilnadu [serial online] 2022 [cited 2022 Oct 3];5:21-4. Available from: http://www.japt.com/text.asp?2022/5/1/21/353744




  Introduction Top


Docetaxel has been a widely used agent against breast, non-small cell lung, gastric, head and neck, and prostate cancer.Although bone marrow suppression, gastroenterological, hepatic, dermatological, endocrine, and neurological side effects are frequently reported, docetaxel/taxane-induced interstitial lung disease (ILD) is a relatively rare occurrence.1–5% of those who receive docetaxel may develop interstitial pneumonitis to a significant degree. The most common effect of docetaxel on the lung is interstitial pneumonitis. Patients may also present with non-cardiogenic pulmonary oedema, pleural effusions, and peripheral oedema as a result of capillary leakage syndrome. Hypersensitivity reaction with angioedema, stridor, or wheezing is also possible. Interstitial pneumonitis has been associated with docetaxel administration, and may progress to respiratory failure and death. This syndrome may occur as early as 1 to 2 weeks after administration of the drug.


  Case Report Top


A 42-year-old female was diagnosed with invasive ductal carcinoma of the breast stage II, TNMC classification pT1cN2aMX. She underwent a modified radical mastectomy on August 3, 2021, followed by four cycles of chemotherapy with adriamycin and cyclophosphamide, which she tolerated well.

In January 2022, in view of HER2 positive, she was shifted to docetaxel- and trastuzumab-based therapy. Within 2 weeks, she developed progressive breathlessness and respiratory failure.

Her chest X-ray [Figure 1]a which was taken in January 2022 before chemotherapy is shown below. The minimal infiltrates seen in the right lower zone were probably attributed to post infective changes since the patient had tolerated chemotherapy well though the possibility of chemotherapy-induced changes could not be ruled out. Post chemotherapy chest X-ray showed bilateral heterogeneous opacity involving all zones [Figure 1]b. Computed tomography chest showed bilateral interstitial pneumonitis [Figure 1]c. Her complete hemogram and routine investigations were within normal limits. COVID reverse transcription-polymerase chain reaction was found to be negative. BAL was done, and infection was ruled out. The pulmonary function test showed a moderate restrictive pattern. DLCO showed moderate reduced diffusing capacity for carbon monoxide. She was treated with oxygen therapy and IV methylprednisolone for 5 days followed by 2 weeks' course of oral steroids. The patient showed dramatic clinical improvement with treatment, and repeat chest X-ray [Figure 1]d showed radiological resolution. The patient, after recovery, was referred back to the medical oncologists for favor of alternate chemotherapy regimens and further follow-up.
Figure 1: (a) Chest X-ray of patient before initiation of chemotherapy showing left mastectomy and normal lung parenchyma. (b) Chest X-ray of patient showing bilateral heterogeneous opacity involving all zones after initiation of chemotherapy. (c) CT chest showing bilateral interstitial pneumonitis after initiation of chemotherapy. (d) Chest X-ray of patient after initiation of treatment with steroids showing partial resolution. CT=Computed tomography

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  Discussion Top


Drug-induced lung damage is a well-known but relatively rare complication of cytotoxic chemotherapy.[1] Various pulmonary and pleural complications have been documented with chemotherapy, including acute lung injury, pulmonary edema, interstitial pneumonitis, and pulmonary fibrosis. Various parenchymal complications of chemotherapy are listed in Table.[2]



Docetaxel is a taxane group of chemotherapeutic agent used widely in various malignancies such as breast, gastric, ovarian, and non-small cell lung carcinoma. Taxane-induced interstitial pneumonitis is a well-recognized toxicity following chemotherapy.[3] Docetaxel binds to β-tubulin and enhances its polymerization. The microtubules are stabilized, and their depolymerization is prevented. Docetaxel induces programmed cell death in cancer cells by binding to an apoptosis-stopping protein called Bcl-2 and thus arresting its function.

A specific pulmonary antigen expressed by the tumor may cause the proliferation of cytotoxic T-cells. In addition, reactive oxygen metabolites have been associated with direct lung injury in docetaxel-induced lung injury.

Merad et al. reported two patients with docetaxel-related pneumonitis who recovered after treatment with corticosteroids.[4] Before concluding that cause for pneumonitis as drug-induced, other causes such as infection, lymphangitis carcinomatosa, other ILD, heart failure should be excluded.[4]

Read et al. reported a case series of four patients with interstitial pneumonitis related to docetaxel.[5]

Trastuzumab is a monoclonal antibody directed against HER2, which is overexpressed/amplified in about 25% of breast cancers.[6]

Taxanes are chemotherapeutic agents commonly used for the adjuvant treatment of HER2-positive breast tumors. The combination of taxanes with trastuzumab led to decreased recurrence rates in patients with high-risk early-stage HER2-positive breast cancer.[7]

Taxane-induced pneumonitis is described in a few case reports and case series with an estimated risk of ~5%.[8]

In most cases reported, patient's adverse effects are seen in those who underwent treatment with trastuzumab in combination with taxanes or had been previously exposed to taxanes prior to initiation of trastuzumab.[9]

The patient presented with interstitial pneumonitis after five cycles of adriamycin and cyclophosphamide and two cycles of trastuzumab and docetaxel as adjuvant treatment. She presented with severe adverse effects requiring hospitalization and promptly responded well to corticosteroid treatment. The patient had worsening of symptoms with decline in forced vital capacity, total lung capacity after combined treatment with trastuzumab and docetaxel. At a later point of time, the patient required oral corticosteroid and showed rapid clinical improvement. This case is similar to many other cases reported in literature cited above, which shows that various drugs can cause interstitial pneumonitis, and budding pulmonologists should be able to identify such complications early and treat promptly to reduce the morbidity and mortality due to drug-induced complications.


  Conclusion Top


Interstitial pneumonitis is a relatively rare but potentially fatal complication of cancer chemotherapy, including taxanes used in the treatment of various malignancies. It is important that this complication is identified and differentiated from other causes of lung infiltrates in malignancy such as infection and managed early so as to reduce the morbidity and mortality due to cancer chemotherapy.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Snyder LS, Hertz MI. Cytotoxic drug-induced lung injury. Semin Respir Infect 1988;3:217-28.  Back to cited text no. 1
    
2.
Michael A Grippi, Jack A Elias, Jay Fishman, Robert Mark Kotloff, Allan I Pack. Pulmonary toxicity related to Chemotherapeutic agents, Fishman's Pulmonary diseases and disorders, 5th Edition, New York: McGraw-Hill Education, [2015] ©2015.  Back to cited text no. 2
    
3.
Anoop TM, Joseph R, Unnikrishnan P, Thomas F, Venugopal M. Taxane-induced acute interstitial pneumonitis in patients with breast cancer and outcome of taxane rechallenge. Lung India 2022;39:158-68.  Back to cited text no. 3
[PUBMED]  [Full text]  
4.
Merad M, Le Cesne A, Baldeyrou P, Mesurolle B, Le Chevalier T. Docetaxel and interstitial pulmonary injury. Ann Oncol 1997;8:191-4.  Back to cited text no. 4
    
5.
Read WL, Mortimer JE, Picus J. Severe interstitial pneumonitis associated with docetaxel administration. Cancer 2002;94:847-53.  Back to cited text no. 5
    
6.
Slamon DJ, Clark GM, Wong SG, Levin WJ, Ullrich A, McGuire WL. Human breast cancer: Correlation of relapse and survival with amplification of the HER-2/neu oncogene. Science 1987;235:177-82.  Back to cited text no. 6
    
7.
Slamon D, Eiermann W, Robert N, Pienkowski T, Martin M, Press M, et al. Adjuvant trastuzumab in HER2-positive breast cancer. N Engl J Med 2011;365:1273-83.  Back to cited text no. 7
    
8.
Chen YM, Shih JF, Perng RP, Tsai CM, Whang-Peng J. A randomized trial of different docetaxel schedules in non-small cell lung cancer patients who failed previous platinum-based chemotherapy. Chest 2006;129:1031-8.  Back to cited text no. 8
    
9.
Kuip E, Muller E. Fatal pneumonitis after treatment with docetaxel and trastuzumab. Neth J Med 2009;67:237-9.  Back to cited text no. 9
    


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