Amenorrhea induced by chemotherapy in Premenopausal Breast Cancer Patients (Retrospective Study)

INTRODUCTION

Breast cancer is the most frequently diagnosed cancer globally and is the leading cause of cancer-related death in women. The American Cancer Society estimates that 249, 260 Americans will be diagnosed with invasive breast cancer and 40, 890 will die of the disease in the United States in 2016. ¹

The treatment of breast cancer includes the treatment of local disease with surgery, radiation therapy, or both, and systemic treatment with chemotherapy, endocrine therapy, biologic therapy, or combinations of these. The need for and selection of various local or systemic therapies are based on several prognostic and predictive factors. These factors include tumor histology, clinical and pathologic characteristics of the primary tumor, ALN status, tumor hormone receptor (ER & PR) content, tumor HER2 status. Adjuvant endocrine therapy is an integral component of care for endocrine-dependent breast cancer (EDBC). The goal of this type of therapy is to counteract the production and the action of oestrogens.²

The ovaries of premenopausal women who received chemotherapy typically have normal to mildly decreased numbers of primordial follicles and a greater decrease in the numbers of maturing follicles,

indicating a greater effect on follicular development than on oocytes. Consistent with these histologic findings are the clinical observations that many women are amenorrhoeic during chemotherapy, often with high serum gonadotrophin concentrations, but that menstrual function and fertility often return several months to years after the cessation of therapy.³

Chemotherapy-induced amenorrhea is a well-recognized side effect of cytotoxic chemotherapy. These drugs appear to have a greater effect on follicular development than on oocytes, with variable degrees of subsequent ovarian dysfunction. Some women develop complete follicular depletion and permanent ovarian failure during chemotherapy, while others may become amenorrhoeic during therapy, but then have subsequent return of ovarian function, menstrual cycles, and fertility, months to years after the cessation of therapy. There are well-recognized risk factors for chemotherapy-induced amenorrhea or ovarian failure, such as age, chemotherapy regimen, subsequent use of endocrine therapy and genetics.⁴

PATIENT AND METHODS

This retrospective study included all patients with breast cancer with at least a minimum follow up of six months after last cycle of chemotherapy either clinically or by E₂ and FSH. Number of patients enrolled in this study is 97 patients from January 2009 to December 2015.

Inclusion criteria: Female patient, Age > 18 years, pathologically confirmed breast cancer, Premenopausal at the diagnosis of breast cancer, Breast cancer at any stage and Six month or more follow up after last cycle of chemotherapy.

Exclusion criteria: Postmenopausal women, Patient with double malignancy, Hysterectomy and Any kind of oophorectomy.

The following data collected from patients’ files: Personal data (age, sex, marital state, sibling), Menstrual history (menarche, regularity), comorbidities (diabetes, hypertension, thyroid dysfunction), contraceptive history, disease criteria (date of first diagnosis, extent of disease, histological type, stage), treatment related data (chemotherapy regimen, number of cycles, regularity), amenorrhea related data (time of amenorrhea, reversibility).

ETHICAL APPROVAL:

Informed consents were obtained from all participants during their follow up at clinic, and data confidentiality was maintained throughout the study and any resulting publication anonymously.

STATISTICAL METHODS:

Amenorrhea defined as absence of menstruation in a woman of reproductive age for more than 6 months either clinically or by E₂ 20>, FSH

RESULTS

Patient’s characteristics:

The mean age of all patients was 41.3 years ranges between (28-54) years. Out of these patients, 93 (95.9%) were married while 4 patients (4.1%) were single. Seventy-seven patients (79.4%) gave history of regular menses while 16 (21.6%) patients had history for irregular menstruation. Table (1), Figure (1)

Fig. 1: Pie diagram shows marital status of patients included in the current study.

Diabetes was observed in 6 patients (6.2%) and 10 patients were hypertensive (10.3 %), while 3 patients (3.1%) were diagnosed with thyroid disorders. Table (1), Figure (2)

 Fig. 2: Histogram shows comorbidities of patients included in the current study.

Histopathological characteristics:

Invasive duct carcinoma diagnosed in 93 patients (95.8%), invasive lobular carcinoma also diagnosed in 2 patients (2.1%), while 2 patients (2.1%) diagnosed with mucinous variant. Table (2), Figure (3)

 MRM done for 55 patients (56.7%) while conservative breast surgery done for the rest of the patients (43.3%). Figure (4)

Eight patients (8.2%) presented with T1 staging, T2 staging found in 60 patients (61.9%), and 19 patients (19.6%) had T3 staging, while 10 patients (10.3%) had T4B disease. Table (2)

Positive estrogen receptors found in 82 patients (84.5%). while rest of patients (15.5%) were negative. Positive progesterone receptor found in 77 patients (79.4%), while rest of patients (20.6%) were negative. Her2neu status was over expressed in 21 patients (21.6%). While 77 patients (78.4%) were negative. Table (2), Figure (5)

*among married

Table 1: Patient characteristics

        Fig. 3: Piediagram shows histopathological characteristics of tumors included in the current study.

Fig. 4: Pie diagram shows type of surgery done for patients included in the current study.

Fig. 5: Histogram shows immunophenotyping pattern of study populations.

Table 2: Histopathological characteristics

Table 3: Induced amenorrhea

SD: standard deviation, p≤0.05 is considered statistically significant, analysis done by independent t test

Table 4: Age of menarche

p≤0.05 is considered statistically significant, analysis done by Chi square test t stage t4B is statistically significant from other stages.

Table 5: Factors in relation with amenorrhea status.

P≤0.05 is statistically significant, CI: confidence interval, NA: not applicable

Table 6: Disease free survival among all patients’ groups