EFFECT OF TAMOXIFEN ON FASTING SERUM LIPID PROFILE IN BREAST CANCER PATIENTS

In contrast to that it has a weak estrogen agonistic effect on liver therapy has favorable effects on serum lipid profile by decreasing serum levels of Total cholesterol and low density lipoprotein (LDL), while its effect on high density lipoprotein (HDL) and triglyceride (TG)is still controversial. So this study is to evaluate the effects of tamoxifenTherapy on fasting serum lipid profile in patients with breast cancer. Results: Mean age was 43.56  3.53yrs , most common BMI was 30-34.9. Patient serum TG levels were raised from baseline after 3 months of tamoxifen with p values of (0.000) we analyzed effects of tamoxifen on serum lipid profile pre and post 3months of tamoxifen .In our study serum Total cholesterol(TC) and low density lipoprotein (LDL) were decreased from baseline after 3months of tamoxifen this is in comparison with studies done by hossein et al,y.hozumi et al and gupta et al, these comparable results are due to SERM effect of tamoxifen and the other factor leading to this effect could be the type of chemotherapy as it is noted that anthracycline based chemotherapy reduces serum TC and LDL [14][8][5][4] and in our patients most commonly anthracycline based chemotherapy was used ,so this could augment the effect of tamoxifen on lowering TC and LDL in our study population.

Breast cancer can be treated with different modalities including surgery, cytotoxic chemotherapy, radiotherapy, endocrine therapy or combination of these modalities. [3] [4] Endocrine therapy for breast cancer targets estrogen and progesterone receptors in breast cancer cells. [5] Tamoxifen is one of the endocrine therapies and has been used as a standard modality for many years. [6] Tamoxifen acts as a selective estrogen receptor modulator by binding to the estrogen receptors on mammary epithelium and blocking the proliferative action of estrogen on mammary epithelium. [7] In contrast to that it has a weak estrogen agonisticeffect on bone,liver and endometrium. [8] In addition to that it has also been observed that Tamoxifen affects various biochemical profiles of the patients including fasting lipid profile and plasma lipoprotein concentrations. [9][10] [11] Tamoxifen therapy has favorable effects on serum lipid profile bydecreasing serum levels of Total cholesterol and low density lipoprotein(LDL), while its effect on high density lipoprotein (HDL) is stillcontroversial. [12]] [14] So this study is to evaluate the effects of tamoxifen Therapy on fasting serum lipid profile in patients with breast cancer.

Objective:-
The objective of this study is To study the effects of Tamoxifen on fasting serum lipid profile of breast cancer patients.

Operational Definition: Fasting Serum Lipid Profile:
Defined as lipid profile of patients taken after overnight fast. It will include LDL, HDL and total cholesterol.

Hormone receptor positive breast tumors:
Defined on the basis of the immuno-histochemical expression of Estrogen receptor (ER) and Progesterone receptor (PR) on biopsy specimen of breast cancer patients.
Methods:-Duration of study: 24 months starting from date of approval.

Ethical approval:
Study was approved by ethical review committee of my institution Sample size: 45 patient were selected that fulfill the inclusion and exclusion criteria of the study.

Sampling Techniques:
Patients enrolled in study using consecutive non probability sampling method. It was a prospective single arm interventional study

Data Collection:
In this study, patients with histological proven carcinoma breast with positive hormone receptor statuswere recruited from Oncology out-patient. After taking an informed consent, selection of patients was carried out on the basis of non-probability consecutive sampling technique. After enrolling the patients in the study, detailed history, examination, and base line fasting serum lipid profile were done. Thereafter, tamoxifen 20mg will be given orally daily for 3 months and fasting serum lipid profile were repeated at 3 months. These results were compared with the baseline fasting serum lipid profile results.
Data Analysis:-SPSS 23 was used to analyze data. Descriptive analysis was done by including frequencies and ranges for qualitative variables like age and gender. Means,range and standard deviationswas used for quantitative variable i.e. fasting serum lipid profile. Statistical analysis was done by paired t-test to compare the baseline and post tamoxifen fasting serum lipid profile levels. p-value of less than 0.05 is taken as significant.

Results:-
Mean age was 43.563.53yrs , most common BMI was 30-34.9.Patient serum TG levels were raised from baseline after 3 months of tamoxifen with p values of (0.000) which was statistically significant while HDL levels were raised but with p value of (0.008 ) which was statistically insignificant. Serum LDL and total cholesterol were reduced from baseline after 3 month with p value of (0.000) and (0.000) respectively.

Discussion:-
Tamoxifen a nonsteroidal antiestrogenic selective estrogen receptor modulator (SERM)synthesized in 1966 was initially developed as an antifertility agent but currently is used as antineoplastic agent in breast carcinoma . As their name says, SERMs are "selective" this means that a SERM that blocks estrogen's action in breast cells can activate estrogen's action in other cells, such as bone, liver, and uterine cells. [4] In our study we analyzed effects of tamoxifen on serum lipid profile pre and post 3months of tamoxifen .In our study serum Total cholesterol(TC) and low density lipoprotein (LDL) were decreased from baseline after 3months of tamoxifen this is in comparison with studies done by hossein et al,y.hozumi et al and gupta et al, these comparable results are due to SERM effect of tamoxifen and the other factor leading to this effect could be the type of chemotherapy as it is noted that anthracycline based chemotherapy reduces serum TC and LDL [14][8][5] [4] and in our patients most commonly anthracycline based chemotherapy was used ,so this could augment the effect of tamoxifen on lowering TC and LDL in our study population. Triglyceride levels (TG) were raised from baseline in our study this can be explained by SERM effect of tamoxifen other factor in my study is baseline raised BMI of patients which could also lead to initially raised TG levels at baseline which strengthens the effect of tamoxifen in altering TG levels in our study it has same results as study done by hossein et al [5] (3) but it has contrasting results with studies done by gupta et al and chilen et al which showed no alteration in serum TG levels this difference could be explained due to apolipoprotein APOE polymorphism .TG levels are modified by APOE polymorphism ,Patients with the APOE4 allele have lower serum TG levels [4] .The genomic differences between races might explain the different TG levels found in this study. APOE 4 levels are lower in western population and high in Asian population [15] which could be reason of baseline raised TG levels in Asian population [15] and could explain raised TG levels in our study .

Selection of cases
HDL cholesterol was raised in my study from baseline but p value was insignificant which is in comparable to studies done previously.  Table 1:-Serum lipid profile in 3months pre and post tamoxifen.

Conclusion:-
Thus my study concludes that tamoxifen has effects on serum lipid profile by increasing TG levels and lowering TC and LDL levels so this should be in consideration while prescribing tamoxifen to the patients having other risk factors for cardiovascular abnormalities .