For most women, advancing age is a major risk factor for breast cancer. In the United States, approximately 230,000 new cases of female breast cancer are diagnosed each year, with almost half of these presenting in older women (usually defined as ≥65 years of age).
Treatment patterns in older women: Worldwide, older women newly diagnosed with breast cancer often receive substandard treatment. In the largest study that included more than 120,000 women, increasing age was associated with the following treatment trends
Declining surgery rates: More than 93% of women under 80 years of age underwent surgery; compared to 83%, 65%, and 41% of patients aged 80-84, 85-89, and ≥90 years, respectively.
Breast-conserving surgery was followed more rarely by adjuvant radiation therapy: the rates were over 90%, 86%, 71%, 36%, and 15% for patients under 75, 75-79, 80-84, 85-89, and 90 years of age or older, respectively.
Increased use of initial endocrine therapy: A greater proportion of female patients receive initial endocrine therapy with increasing age. This proportion went from <1% in women under 65 years of age to 47% in patients 90 years and older.
The difference in treatment patterns between older and younger women may be due to differences in breast cancer characteristics, the presence of competing co-morbidities, and general health status.
In addition, older women are often not enrolled in clinical trials evaluating breast cancer treatment, in part because inclusion criteria may have excluded them for a variety of reasons. As a result, there is a lack of evidence-based medical guidelines to inform the treatment of breast cancer for this group.
Factors influencing treatment decisions: The high proportion of inert tumor types in older women with breast cancer and/or the presence of other potentially life-threatening medical co-morbidities may explain treatment trends in this group that can omit some of the standard components of breast cancer treatment. These include.
Tumor biology: The incidence of tumors with more inert features was higher in older women than in younger women in most studies. For example, older breast cancers have a lower proliferative index, normal P53 expression and diploid DNA compared to younger women, according to the SEER registry analysis. other differences include
Higher expression of hormone receptors: older women with breast cancer typically have more expression of estrogen receptors (ER) and/or progesterone receptors (PR) than younger women.
Human epidermal growth factor 2 receptor (HER2) overexpression is lower: HER2 gene amplification is less common in older women. However, as in younger women, HER2 overexpression is associated with poor prognosis.
Higher proportion of tumors with low-grade histologic features: As in younger women, invasive ductal carcinoma is the most common tissue type in the older breast cancer population. However, more inert breast cancers (such as mucinous and papillary carcinomas) tend to be more common with advancing age.
General health status: Life expectancy, co-morbidities and functional status are important factors to consider in elderly breast treatment decisions. In general, advanced age is associated with reduced tolerance of physical stress, higher prevalence of co-morbidities, reduced social support (e.g., transportation), and impaired and frail cognitive function. Any of these factors can alter the risk-benefit balance considered in the treatment of breast cancer.
Life expectancy: Breast cancer does not necessarily result in death in older women due to the possible presence of other competing causes of death. Therefore, a woman’s life expectancy should be considered when developing a treatment plan.
Co-morbidities: In the presence of co-morbidities, the life expectancy of women with breast cancer is almost halved.
Functional status: Patients with poorer functional status may be at greater risk of dying from causes other than breast cancer, suggesting that such patients may not benefit from breast cancer treatment.
Frailty: In older breast cancer patients, frailty is associated with an increased risk of treatment-related complications, including a greater likelihood of requiring hospitalization and shorter overall survival.
Treatment: The following treatment options are recommended for older women
For healthy older women, treatment according to the standard guidelines for breast cancer is recommended. In general, healthy older women and younger patients tolerate breast cancer treatment well and do not have an increased risk of complications.
For medically frail patients (e.g., cognitive impairment, frailty, and/or presence of co-morbidities), treatment depends on whether surgery is an option
For patients suitable for surgery, surgery to remove the primary tumor is preferred over medical treatment.
For patients who refuse surgery or are not candidates for surgery, initial medical therapy is offered based on primary tumor characteristics; however, supportive or palliative care is recommended for patients with limited life expectancy and a desire to avoid associated treatment toxicity.
Initial radiation therapy should not be used.
The approach to systemic therapy for older women depends on the general health status of the individual patient, whether surgery has been performed and the presence of risk factors (e.g., high tumor grade, lymph node involvement, vascular nerve invasion, or high-risk gene expression analysis). Options for systemic therapy include chemotherapy and/or endocrine therapy. For HER2-positive women, this also includes the application of targeted agents.
Better medical situation: The treatment of older healthy women newly diagnosed with non-metastatic breast cancer is identical to that of younger women and should include surgical removal of the breast tumor, axillary evaluation (if needed), radiation therapy and systemic adjuvant therapy.
Breast surgery: Standard surgical treatment should be given to older healthy women who are in good medical condition. Most will opt for breast-conserving surgery rather than mastectomy. However, patients with large tumors that cannot be treated by breast-conserving surgery are best treated by mastectomy. Neoadjuvant systemic therapy may be considered for some patients.
Axillary management: The surgical options for axillary lymph nodes are similar to those for younger women.
Role of radiotherapy: Radiotherapy is usually well tolerated and the breast looks good, even in older women. However, in general, older women have a lower risk of local recurrence, and the benefit of radiation therapy after breast-conserving surgery may decrease with age. Therefore, some older women may not require radiotherapy, especially those who are older than 70 years, have small primary tumors (<2 cm) with positive ER, no clinical or pathologically confirmed evidence of lymph node metastases, and who agree to adjuvant endocrine therapy. Patients who do not wish to receive adjuvant radiotherapy should be informed that they are at higher risk of recurrence in the breast than those who receive radiotherapy.
Adjuvant systemic therapy: Options for systemic therapy include chemotherapy, and/or endocrine therapy. In addition, anti-HER2-targeted therapy is part of the treatment for HER2-positive individuals.
Chemotherapy: The principles of chemotherapy are the same as for young women. Chemotherapy regimens are anthracycline-based and/or violet-shirt-based in most cases; for patients unsuitable for anthracyclines, doxorubicin + cyclophosphamide, or oral CMF regimens may be considered; capecitabine alone orally is generally not recommended as an adjuvant chemotherapy regimen.
Endocrine therapy: Regardless of age, endocrine therapy should be considered in all ER-positive patients with primary tumors >5 mm. Treatment with aromatase inhibitors (AI) is preferred because of the better benefit of taking AI compared to tamoxifen. Tamoxifen alone is a reasonable alternative for women at risk of cardiovascular complications or bone loss and for those patients who cannot tolerate AI due to toxicity. Endocrine therapy for at least 5 years and up to 10 years of therapy may also be appropriate for selected patients, especially those with high-risk tumor features (e.g., positive lymph nodes, or high tissue grading).
Medically frail: For medically frail patients (e.g., with cognitive dysfunction or co-morbidities), the risks of surgery, chemotherapy, endocrine therapy, and radiation must be considered when developing an individualized treatment plan. Supportive care or palliative care should be offered to patients with limited life expectancy and a desire to avoid treatment-related toxicity.
For those suitable for surgical treatment: surgery is preferred over medical treatment. However, initial endocrine therapy is also a reasonable option for ER-positive patients.
Those who are not suitable for surgery: systemic therapy is given based on the primary tumor characteristics. For ER-positive patients, initial endocrine therapy can be given; for ER-negative patients, single-agent chemotherapy; for HER2-positive patients, Herceptin therapy can be added.
Initial endocrine therapy for ER-positive individuals: AI therapy is preferred; tamoxifen is also a reasonable alternative option for women who cannot tolerate AI therapy.
Initial radiotherapy: Rarely used as the only treatment. Radiotherapy may be considered if surgery is not possible due to co-morbidities and frailty, endocrine therapy is not effective against the tumor, and local control is necessary for symptom relief. Medium to high doses are usually needed to control locally advanced breast cancer not treated with surgery, and radiotherapy increases the risk of local toxicity.