How do Breast Cancer Treatments Affect Fertility?

Breast cancer is the most common cancer diagnosed in women, accounting for more than 1 in 10 new cancer diagnoses each year. It is the second most common cause of death from cancer among women in the world.

Genesis

Breast cancer, like any other cancer of the reproductive system, develops due to DNA damage and genetic mutations that can be impacted by exposure to estrogen. Scientists reports several genetic mutations that bring with it an increased risk of breast cancer. Two such major genes are BRCA1 (located on chromosome 17) and BRCA2 (located on chromosome 13). Consequently, the family history of ovarian or breast cancer builds the gamble for breast cancer progression.

Diagnosis

The majority of the patients find this disease during routine screening. Health care providers may further find a breast lump, change of breast shape or size, or nipple discharge stipulating an abnormality in the breast parenchyma. In any case, mastalgia is commonly expected. Actual examination and imaging, particularly mammography, and tissue biopsy should be used to diagnose breast cancer. The survival rate improves with early diagnosis.

Ultrasonography is useful in assessing the consistency and size of breast lumps. It has a great role in guided needle biopsy. Magnetic resonance imaging has good sensitivity for detecting anomalies in soft tissues, including the breast. The growth will spread lymphatically and hematologically, prompting far-off metastasis and poor prognosis.

Repercussions

If breast cancer progression goes beyond control, it may cause symptoms in different systems of the body. Affected areas may include:

• Lymphatic System: Tumors may spread to the lungs and liver through the lymphatic system.
• Liver: One may experience symptoms specifically jaundice, severe abdominal bloating, and, edema (fluid retention).
• Skin: Some women also experience dimpling of the skin along their breasts and some experience peau d’orange appearance. Thickening of breast tissue is also common in breast cancer.
• Bones and muscles: Extensive metastasis can affect muscles and bones too. Such effects can also increase risk for injuries due to a lack of mobility. Weak bones can also be a reason for fractures.
• Physical changes: excessive fatigue, weakness, appetite loss, unintentional weight loss
• Reproductive system: Breast cancer patients treated with chemotherapy may develop premature ovarian failure or very early menopause. Almost four out of five women treated with cyclophosphamide, an often-prescribed chemotherapy drug for treating breast cancer, develop ovarian failure.

Cancer treatments and its after effects

Cancer treatments are essential for future health, but they tend to damage reproductive organs and glands that control fertility. Changes to a patient’s fertility may be temporary or permanent.

Ovarian ablation has been recently devised as a management approach for breast cancer. There are several techniques of ovarian ablation such as radiation-induced ablation, surgical removal of ovaries, and chronic utilization of luteinizing hormone-releasing hormone (LHRH) analogs. Moreover, some experts recommend that cytotoxic chemotherapy could be performed by inducing ovarian ablation in premenopausal females with breast cancer.

Chemotherapy: These can be toxic to primordial follicles, as they break DNA strands, induce apoptosis, and reduce stromal function within the ovary. Some damaging chemotherapies include alkylating chemotherapies, such as cyclophosphamide, busulfan, melphalan, and procarbazine. All of these drugs act on ovaries, and delays the release of eggs and estrogen causing ovarian insufficiency (POI).

Radiation therapy: The ovarian reserve is sensitive to pelvic radiation as it may destroy the majority of immature ovarian follicles or significantly reduce follicle number. This reduction may cause immediate loss of fertility or early-onset infertility and menopause after cancer treatment. Radiation to the brain can also harm the pituitary gland. This gland is important because it sends signals to the ovaries to make estrogen which is needed for ovulation. The amount of radiation given and the part of the body being treated plays a role in whether or not fertility is affected.

Hormone therapy: Despite being used to treat cancer, it can disrupt the menstrual cycle, which in turn affects fertility. Side effects depend on the specific hormones used and normally include hot flashes, night sweats, mood changes, and vaginal dryness.

Preserving Fertility

Preserving fertility before or during cancer treatment in young women is a grave medical problem due to delayed motherhood and improved survival rates. Diagnosing breast cancer in young women poses a threat to fertility. Due to a recent trend of delaying pregnancy, an increasing number of breast cancer patients of reproductive age wish to bear children. Health care providers should be able to oversee fertility issues in cancer survivors.

The main concept behind Fertility Preservation is to advise patients on the most proficient method to gauge the dangers and advantages of maintaining fertility. Both the health care provider and the patient must be aware of the choices, the associated dangers, and the probability of progress.

Cryopreservation :

1. Embryo cryopreservation: It is considered the standard method of fertility preservation among young women facing gonadotoxic chemotherapy. Embryo cryopreservation follows the procedure used in infertile patients for in vitro fertilization.
2. Tissue cryopreservation: Cryopreservation of the ovarian cortex is an efficient way of preserving ovarian function, at least theoretically. In this method, ovarian tissue is resected prior to chemotherapy, cryopreserved, and retransplanted upon treatment completion. Depending on the part of the tissue to be removed, a cortical strip or the whole ovary may be resected. Also, depending on the location of the transplant, orthotopic or heterotrophic transplantation may be performed.

Ovarian Stimulation:

The ovaries are stimulated with gonadotropic hormones to acquire multiple oocytes, and then gonadotropin-releasing hormone (GnRH) agonists or antagonists are administered to inhibit early ovulation.

Ovarian transposition:

It is an effective surgical procedure used to safeguard ovarian function before delivering high doses of radiation therapy. Ovarian transposition has lately been performed in patients whose treatment includes pelvic radiotherapy as a part of management for various gynecologic malignancies.

Tamoxifen:

A drug traditionally used to prevent breast cancer reoccurrence, was recently found to stimulate ovaries in breast cancer survivors during an IVF cycle, enhancing both egg and embryo production. This extra boost can combat infertility barriers such as age and the diminishing ovarian reserves, which occur naturally with aging.

Other combination methods: 

A supraphysiologic level of estradiol during fertility preservation, including controlled ovarian stimulation (COS), might stimulate the proliferation of breast cancer cells. Administration of letrozole as an aromatase inhibitor before and after ovarian stimulation has also proven to be a feasible option.

Conclusion

Signs of progress in Assisted Reproductive Technology have made fertility preservation a more practical choice for patients with cancer. One of the principal concerns of oncologists and oncologic surgeons is that fertility conservation could viciously influence tumor progression. In particular, estrogen-dependent tumors could develop and progress as serum estradiol levels rise with gonadotropin treatment. However, stimulation protocols that make use of aromatase inhibitors like letrozole, keep serum estradiol near physiologic levels during the cycle and therefore have been effectively implemented.

Author:

 Dr. Prachi Sinha is an MBBS graduate from Smt. N.H.L Municipal Medical College, Ahmedabad. She makes her home currently in Ahmedabad with her family, a tiny undisciplined garden, and a growing number of incomplete baking projects. She has garnered much acclaim for her animal activism and adoption drives across Ahmedabad. When she is not working in the hospital, Prachi spends most of her time conducting online webinars for unprivileged women and catching her treasured Bollywood movies. An admitted food fanatic, she feeds her addiction to sushi by taking on her favorite sushi joints on Sunday afternoons