Breast cancer post-menopause: unique challenges and considerations

Breast cancer is a multifaceted illness defined by an uncontrolled growth of abnormal cells within the breast tissue. About 2.3 million people were diagnosed with cancer in 2022, and there were 670000 cancer-related deaths, and it is the most common cancer among women worldwide and a leading cause of cancer-related deaths¹.

Each breast cancer subtype has unique traits, prognoses, and treatment modalities, emphasizing the significance of a precise diagnosis and individualized care plans. Early detection through screening mammograms and self-examinations can improve treatment outcomes². Treatment options vary according to the stage and type of breast cancer but often include surgery, chemotherapy, radiation therapy, hormone therapy, targeted therapy, or a combination of these³.

Recent advancements in molecular diagnostics have enabled personalized treatment approaches, which allow clinicians to direct therapies according to the unique features of each patient’s tumor⁴. Despite treatment progress, breast cancer remains a significant public health challenge, and this emphasizes the importance of ongoing research, awareness, and access to quality care.

Postmenopausal women constitute a distinct demographic in the breast cancer landscape, marked by hormonal changes that can influence disease progression and treatment response. HR+ breast cancer, characterized by the presence of hormone receptors for estrogen and progesterone, emerges as the predominant subtype among this group⁵. These receptors fuel cancer growth and necessitate interventions blocking or disrupting hormonal signaling pathways.

The relationship between age at menopause and breast cancer risk is a topic of considerable interest in the field of oncology. While menopause itself does not inherently elevate the risk of breast cancer, age emerges as a significant factor influencing disease susceptibility for various reasons. About 80% of those with breast cancer are individuals more than 50 years of age⁶. Thus, a correlation exists between menopausal status and breast cancer risk, but it is essential to recognize breast cancer is a complex disease and can arise from a multitude of reasons and risk factors.

Several of these risk factors contribute to the development of breast cancer across all age groups. These include genetic predisposition, family history, lifestyle factors such as alcohol consumption and exposure to radiation, obesity, and lack of physical activity⁷. Understanding these common risk factors provides a foundation for assessing individual risk profiles and implementing preventive measures⁸.

Some of these risk factors may manifest or intensify with age, which can contribute to the increased incidence of breast cancer among older women. These include prolonged exposure to estrogen over a lifetime from early menarche and late menopause⁹, late age at first childbirth. Dense breast tissue is also more prevalent in postmenopausal women, which can accentuate their susceptibility to breast cancer^10.

Additionally, taking breast cancer type into consideration is essential, as there are various subtypes, grades, and stages of breast cancer, all of which are characterized differently and arise from different reasons. For example, endogenous ovarian hormones play a significant role in estrogen receptor-positive (ER+) disease than estrogen receptor-negative (ER-) disease, and they are more pertinent for lobular than ductal tumors⁹.

Disparities in risk factors between premenopausal and postmenopausal women underscore the complexity of breast cancer etiology. With advancing age and the onset of menopause, hormonal fluctuations also play an important role in shaping breast cancer risk. Postmenopausal women experience a decline in estrogen and progesterone levels, which can influence tumor biology and the development of hormone receptor-positive (HR+) breast cancers¹¹.

So while menopause itself does not directly elevate breast cancer risk, age can serve as a proxy for cumulative exposure to various risk factors. The interplay between hormonal changes, age-related factors, and individual risk profiles also underscores the relationship between age at menopause and breast cancer risk.

Breast cancer is a complex disease, with no two patient profiles being the same. While there is plenty of medical research done on its origin and development and their correlation with age, each case is unique and should be treated as such.

Postmenopausal breast cancer patients confront particular challenges that inform their diagnosis, treatment, and survival. Many of these challenges stem from their hormonal status and any age-related health concerns, on top of the psychological and emotional challenges that all breast cancer patients experience.

What is menopause?

Menopause marks the permanent cessation of menstruation, primarily diagnosed retrospectively after 12 consecutive months without a menstrual period. On average, women in the United States experience menopause around the age of 51, with most entering this stage between 49 and 52 years old. Premature menopause occurs before the age of 40 years¹².

Symptoms associated with menopause

The symptoms associated with menopause predominantly stem from estrogen deficiency, and they may arise in the form of mood swings, vaginal dryness, and hot flashes, the latter characterized by sudden feelings of warmth, sweating, and flushing of the face and upper body¹³.

Osteoporosis, a disorder marked by a reduction in bone mass., is also a concern during menopause due to a drop in estrogen concentration, which increases the risk of fractures and bone-related injuries. Body composition and weight changes are common challenges, often resulting in frustration and decreased self-esteem¹³.

However, menopausal symptoms can vary widely among individuals, which makes it challenging to find effective management strategies, especially among breast cancer patients. Women may encounter difficulties finding definitive treatment options and the most suitable approach for their specific needs.

Overall, the challenges of menopause and, more significantly, postmenopausal breast cancer women can cause significant physical discomfort, emotional distress, and lifestyle adjustments that require comprehensive support and understanding from healthcare providers, partners, and peers¹².

Breast cancer recurrence in postmenopausal women

Postmenopausal women may also have a more significant chance of late-stage disease recurrence than their premenopausal counterparts, depending on their menopausal status at diagnosis. Studies have shown that for women with earlier age at menopause who have experienced ER+ and/or PR+ stage I-III breast cancer were more likely to develop metastatic breast cancer (advanced breast cancer)¹⁴. This calls for continued attention and monitoring even years after the first course of treatment is over.

Treatment for postmenopausal breast cancer women is multifaceted and individualized to the patient’s needs, taking into account variables other than age, such as the stage and grade of breast cancer, general health, and treatment accessibility. Common options for postmenopausal women who have HR-positive breast cancer include:

Endocrine therapy

Endocrine therapy is fundamental in treating hormone receptor-positive (HR+) breast cancer in older women (postmenopausal women)¹⁵. This therapy targets the hormone receptors that fuel cancer growth. Aromatase inhibitors (AIs) like letrozole and anastrozole and selective estrogen receptor modulators (SERMs) such as tamoxifen are frequently used. Tamoxifen works by blocking estrogen receptors, thereby inhibiting cancer cell proliferation¹⁶. AIs, on the other hand, reduce estrogen production in postmenopausal women, depriving the cancer cells of the hormone they need to grow.

Hormone therapy is frequently used as adjuvant therapy after surgery to lower the risk of cancer recurrence. In some cases, it may be initiated before surgery as neoadjuvant therapy. Usually, hormone therapy is continued for a minimum of 5 years, however, in situations where there is a higher risk of cancer recurrence, treatment duration exceeding five years might be recommended for certain women¹⁷.

Chemotherapy

Chemotherapy is an essential component in the treatment of postmenopausal women with breast cancer. This treatment involves using medications to destroy cancer cells or slow their growth. It can be taken orally or through the intravenous route18. Not all breast cancer women will need chemotherapy.

After surgery, adjuvant chemotherapy is administered to eradicate any cancer cells not removed during the procedure or that have spread to other areas of the body and were not visible on imaging. When a patient has a large tumor and is a good candidate for surgery, chemotherapy is administered in advance of the procedure to help the cancer become smaller. This kind of chemotherapy is called neoadjuvant.

Common chemotherapy agents include anthracyclines like doxorubicin and taxanes such as paclitaxel. Anthracyclines work by interfering with DNA replication, which ultimately leads to cancer cell death. Taxanes, on the other hand, disrupt cell division, preventing tumor growth¹⁸.

While chemotherapy can be effective, it may also cause side effects like nausea, hair loss, and fatigue. These side effects can usually be managed through supportive care measures. For postmenopausal women with breast cancer, chemotherapy is frequently used in conjunction with other treatments such as radiation therapy, targeted therapy, and surgery to improve treatment outcomes¹⁸.

Monitoring through tests and scans

A crucial part of the management approach for postmenopausal breast cancer women is routine monitoring through tests and imaging. With monitoring tools, medical professionals may evaluate the efficacy of treatment, spot any indications of cancer recurrence, and identify any possible adverse effects of the medication.

Mammograms, MRIs, X-rays, and PET scans are common imaging modalities utilized for monitoring. By using these imaging procedures, medical professionals can see any alterations in the breast tissue or identify any malignant cells that may be present in other body parts¹⁹. Blood testing for tumor markers, liver function test and biopsy for metastatic disease, complete blood count, and renal function test may be performed in addition to imaging examinations to track the course of the disease, metastasis, and complications from the treatments. By consistently monitoring the patient’s condition using various tests and scans, medical professionals can make well-informed judgments regarding therapy modifications and deliver individualized care to enhance treatment outcomes.

Breast cancer presents unique challenges for postmenopausal women, and postmenopausal breast cancer patients are not a monolith. Tailored approaches to diagnosis and treatment options for the disease are required, and survivorship depends on each individual case.

A common misconception is that age is a risk factor for breast cancer, but while it is correlated with certain types of cancer, it is closer to reality to say that age can exacerbate risk factors that cause cancer, which produces their correlation.

For older patients, menopausal symptoms alongside cancer treatment can also often add to their challenges in fighting the disease. Personalized care plans and comprehensive support are essential to address changes in hormone levels and other age-related conditions such as osteoporosis. Ensuring postmenopausal women receive the required care and support throughout their breast cancer journey can start by increasing awareness around the issue and removing stigma around the conversation.

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