Thyroid functions consequences following adjuvant chemotherapy for breast cancer after mastectomyHany Khairy Mansour* and Laila Mahmoud Ali Hendawy
Hany Khairy Mansour, Department of Internal Medicine and Endocrinology, Faculty of Medicine, Ain Shams University, Egypt,
Received: 01-Nov-2021, Manuscript No. M-OAR-22-46348 ; , Pre QC No. OAR-22-46348 (PQ) ; Editor assigned: 11-Nov-2021, Pre QC No. OAR-22-46348 (PQ) ; Reviewed: 25-Dec-2021, QC No. OAR-22-46348 (Q) ; Revised: 12-Mar-2022, Manuscript No. OAR-22-46348 (R) ; Published: 19-Apr-2022
The goal: It is to evaluate the effect of adjuvant chemotherapy on thyroid function in women with diagnosed breast cancer after radical mastectomy and prior to radiotherapy.
Patients and interventions: Forty Egyptian women with age ranging from 18 to 60 years who adminstered 5-flourouracil, epirubicin and cyclophosphamide as adjuvant therapy for breast cancer after mastectomy and prior to radiotherapy. Free T3, Free T4, TSH, anti-thyroglobulin antibody and thyroid peroxidase antibody were evaluated prior and after 6 cycles of treatment with chemotherapy.
Results: There were highly statistically significant difference in TSH p=0.005 being higher after chemotherapy, also in free T4 values P=0.025 being lower after chemotherapy. There was no statistically significant difference in free T3 P=0.051, Concerning both anti-thyroglobulin and anti-peroxidase there was no change in values before and after chemotherapy.
mastectomy, breast cancer, adjuvant chemotherapy
Breast cancer is the most frequent malignancy and theleading cause of death from malignancies amongwomen [1,2]. It was reported that incidence of this cancerin developed countries is more than that in developing countries. Treatment modalities for thiscancer include surgery, radiation therapy, chemotherapy, and hormone therapy .
Chemotherapy can be applied asadjuvant or neoadjuvant treatment. Adjuvant che- motherapy is considered as a gold standard therapy for many patients with breast cancer at high risk early stage [4,5]. Thyroid hormones, which act in cell development,growth, differentiation, and metabolism, are adjusted by hypothalamic�?�pituitary axis. It seems thatin patients with cancer, thyroid function is found to bevulnerable to chemotherapeutic drugs, as hypothalamic�?�pituitary axis is active and this treatment modality is asystemic therapy for the patients .
Cytotoxic agents may render the thyroid gland sensitive to the effects of concomitant radiation therapy, increasing the risk of primary hypothyroidism due to radiation, Some agents such as mitotane, 5-fluorouracil, estrogens, tamoxifen, podophyllin, and L-asparaginase alter levels of thyroid hormone-binding proteins without clinical significance . Several epidemiological studies show a positive association between plasma thyroid hormones (TH)-triiodothyronine (T3) and the prohormonethyroxine (T4)-levels and breast cancer risk, which supports the notion that THpromote tumor growth . Definitely, in patients with hypothyroidism, breast cancer is diagnosed at an older age and in earlier stage, suggesting that hypothyroidism protects against breast cancer and is associated with more indolent disease .
GOAL OF THE STUDY
To evaluate the effect of adjuvant chemotherapy on thyroid functions in women with breast cancer after radical mastectomy and prior to radiotherapy.
MATERIAL AND INTERVENTIONS
Our prospective interventional study was performedin the period from March to September 2019 on forty Egyptian women 18-60 years old who administerted 5-flourouracil, epirubicin and cyclophosphamide for a dianosed breast cancer after radical mastectomy and prior to radiotherapy selected from oncology out-patient clinic at Ain Shams University Hospital.
Our study was approved by a Ain Shams University, Faculty of medicine Research Ethics Committee FWA 000017858 independent ethical committee.
Patients with thyroid functions abnormalities prior to treatment, Patients received previous neck irradiation, Patients with sick euthyroid illness prior to treatment.
All patients were subjected to the following
Full history taking. Thorough clinical examination emphasizing on pulse, blood pressure weight, neck examination, Laboratory investigations including: Free T3, Free T4, TSH Prior to treatment and after the last cycle after 6 months, thyroid peroxidase antibody and antithyroglobulin antibody before and after treatment.
Data were collected, revised, coded and entered to the Statistical Package for Social Science (IBM SPSS) version 23. The quantitative data were presented as mean, standard deviations and ranges when their distribution foundparametric.The comparison between two paired groups with quantitative data and parametric distribution were done by using Paired t-test.
It was found a high significant increase in TSH (p=0.005), significant decrease in free T4 values (P=0.025) with no statistically significant difference in free T3 value (P=0.051) as shown in Tables (1,2,3). Regarding both antithyroglobulin and antiperoxidase antibodies there was no statistically significant difference in values before and after chemotherapy.
According to our study we found that there was high significant difference between TSH values before and after chemotherapy (p=0.005) being higher after the adjuvant therapy with statistically significant decrease in unbound T4 values (p ≤ 0.05) and decrease in free T3 value which was of no statistical significance (p=0.051).
This was constant with Desai et al. who found that cyclophosphamide caused hypothyroidism in thirty six percent of patients. Twenty percent of patients had clinically significant thyroid impairment as documented by elevated serum TSH concentration. Their data suggest that the incidence of hypothyroidism increases with the duration of cyclophosphamide therapy. This may explain the higher incidence of hypothyroidism in their study compared with the 4% to 7% occurrence cited in earlier reports in which this agent was used for shorter periods .
Also Mannavola et al. in their study on cyclophosphamide showed similar results as ours with decreased free T3 and T4 and increased TSH. Hypothyroidism was documented in 46% of patients and a transient elevation of TSH levels in another 25% of cases. Thus, the overall prevalence of elevated TSH levels after cyclophosphamide was 71%, in accordance with recent reports .
Several potential mechanisms of cyclophosphamide induced thyroid dysfunction have been proposed. Desai et al. suggested destructive thyroiditis because of the high incidence of transient thyrotoxicosis prior to developing hypothyroidism .
The increase of TSH value observed in our study (2.42 mU/ L before chemotherapy vs. 2.87 mU/L after chemotherapy) could also be explained in the context of recovery of ‘‘Non Thyroidal Illness’’ (NTI), an adaptive response to (chemotherapy- induced) cellular damage. In critically ill patients, the hypothalamus-pituitary-thyroid axis downregulates as an adaptation to adverse physical conditions .
Tab.1. Comparison between TSH values for studied group before and after chemotherapy
|TSH (mU/L)||Before No= 40||After No. =40||Test value||P value|
|Range||0.7-4.2||1.2 – 4.2|
Tab.2.Comparison between fT3 values for studied group before and after chemotherapy
|Free T3 (pg/ml)||Before No = 40||After No =40||Test value•||P value|
|Mean±SD||2.68±1.01||2.58 ± 0.93||2.01||0.051|
|Range||1-4.4||1 – 4.3|
Tab.3.Comparison between fT4 values for studied group before and after chemotherapy
|Free T4 (ng/dl)||Before No= 40||After No=40||Test value||P value|
|Mean±SD||1.32±0.50||1.23 ± 0.46||2.326||0.025|
|Range||0.2-2.5||0.2 – 2.5|
Endocrine disorders are among the most commonly reported long-term complications of cancer treatment .
Thyroid disorders include a broad variety of pathophysiological mechanisms;it may be subtle in presentation, sometimes hardly identified, and even more difficult to relate to a specific chemotherapeutic regimen due to the little specific wide clinical trials .
According to our study, there was decline of fT4 (p=0.025) and this was constant with Khalili, et al. who found that the large reduction of circulating fT4 is associated with less side effects of treatment, but can lead to clinical symptoms of hypothyroidism and rarely life threatening complications . The effect of thyroid hormones on chemotherapeutic efficacy rarely researched before, and whether adding thyroid hormones during chemotherapy is suitable for breast cancer patients is still unknown. Some researchers found hypothyroidism may be the protective element for cancers, as hypothyroidism can inhibit tumor growth .
Summary and Conclusion
So, from our study we can conclude that cytotoxic drugs that are still widely used as adjuvant chemotherapy in multiple types of cancer patientscan cause alterations in thyroid function by different mechanisms. In our study these alterations didn’t reach the value of overt hypothyroidism, so, longer duration of follow up is needed to detect these changes early to avoid adverse outcomes. Also, follow up of thyroid functions before and after chemotherapy is recommended.
- Farhood B, Geraily G, Alizadeh A. Incidence and mortality of various cancers in Iran and compare to other countries: areview article. Iran J Publ Health. 2018;47:309‐316. [Google Scholar]
- Ferlay J, Soerjomataram I, Dikshit R, Eser S, Rebelo M, et al. Cancer incidence and mortality worldwide: sources, methods and major patternsin GLOBOCAN 2012. Int J Cancer. 2015;136:E359‐E386.
- Farhood B, Mahdavi SR, Emranpour MH, MohammadiAsl K, Nekoui N, et al. Skin reaction in radiation therapy for breast cancer. Iran J Med Phys. 2014;11:316‐321.
[Google Scholar] [CrossRef]
- Goldvaser H, Ribnikar D, Majeed H, Ocaña A, Amir E. Absolute benefit from adjuvant chemotherapy in contemporary clinical trials: A systemic review and meta‐analysis. CancerTreat Rev. 2018;71:68‐75.
- Group EBCTC, Peto R, Davies C, Gray R, Pan HC, et al. Comparisons between different polychemotherapy regimens for early breast cancer: meta‐analyses of long‐term outcome among 100 000 women in 123 randomised trials. Lancet. 2012;379:432‐444.
- Khan MA, Bhurani D, Agarwal NB. Alteration of thyroidfunction in Indian HER 2‐negative breast cancer patientsundergoing chemotherapy. Asian Pac J Cancer Prev. 2015;16:7701‐7705.
- Kailajarvi M, Ahokoski O, Virtanen A, Salminen E, Irjala K. Alterations in laboratory test results during adjuvant breast cancer treatment. Clin Chem Lab Med. 2000;38:443-451.
- Moeller LC, Fuhrer D. Thyroid hormone, thyroid hormone receptors, and cancer: a clinical perspective. Endocr Relat Cancer. 2013;20:R19-R29.
- Cristofanilli M, Yamamura Y, Kau SW, Bevers T, Strom S, et al. Thyroid hormone and breast carcinoma. Primary hypothyroidism is associated with a reduced incidence of primary breast carcinoma. Cancer. 2005;103:1122-1128.
- Stava CJ, Jimenez C, Vassilopoulou-Sellin R. Endocrine sequelae of cancer and cancer treatments. J cancer Surviv. 2007;1:261-74.
- Yeung SC, Chiu AC, Vassilopoulou-Sellin R, Gagel RF. The endocrine effects of nonhormonal antineoplastic therapy. Endocr Rev. 1998;19:144-172.
- Desai J, Yassa L, Marqusee E, George S, Frates MC, et al. Hypothyroidism after cyclophosphamide treatment for patients with gastrointestinal stromal tumors. Ann Intern Med. 2006;145:660-664.
- Mannavola D, Coco P, Vannucchi G, Bertuelli R, Carletto M, et al. A novel tyrosine-kinase selective inhibitor, cyclophosphamide, induces transient hypothyroidism by blocking iodine uptake. J Clin Endocrinol Metab. 2007;92: 3531-3534.
- Warner MH, Beckett GJ. Mechanisms behind the nonthyroidal illness syndrome: an update. J Endocrinol. 2010;205:1-13.
- Khalili M and Wong RJ. Underserved does not mean undeserved: unfurling the HCV care in the safety net. Dig Dis Sci. 2018;63:3250-3252.