Which types of cancer in women in their 20s primarily require chemotherapy as a first-line treatment?

Cancers in Women in Their 20s That Primarily Require Chemotherapy

In women in their 20s, triple-negative breast cancer, HER2-positive breast cancer, and advanced ovarian cancer (stage II-IV) are the primary cancers requiring chemotherapy as first-line treatment. 1, 2

Triple-Negative Breast Cancer

All triple-negative breast cancers benefit from adjuvant chemotherapy, with the possible exception of very low-risk special histological subtypes such as medullary or adenoid cystic carcinomas. 1

• Standard regimens consist of 4-8 cycles of anthracycline- and/or taxane-based chemotherapy, with sequential administration of anthracyclines followed by taxanes being the recommended approach. 1
• The majority of triple-negative patients (88%) undergo neoadjuvant chemotherapy first. 3
• For stage II-III triple-negative disease, the addition of carboplatin to neoadjuvant paclitaxel followed by AC improves event-free survival. 2
• The addition of neoadjuvant pembrolizumab to paclitaxel plus carboplatin chemotherapy followed by EC/AC improves event-free survival in stage II-III triple-negative breast cancer. 2

HER2-Positive Breast Cancer

All HER2-positive tumors require chemotherapy combined with trastuzumab, regardless of hormone receptor status. 1

• One year treatment with adjuvant trastuzumab, together with chemotherapy, is indicated for women with HER2-positive, node-positive or high-risk node-negative breast cancer (tumor size > 0.5 cm). 2
• Trastuzumab should be administered concurrently with taxanes (not anthracyclines) and continued for one year total. 1
• Trastuzumab combined with chemotherapy approximately halves recurrence risk and improves overall survival compared to chemotherapy alone. 1
• For HER2-positive/hormone receptor-positive (triple-positive) disease, use anthracycline-taxane sequence plus trastuzumab plus endocrine therapy. 1

Ovarian Cancer (Epithelial, Primary Peritoneal, Fallopian Tube)

Most patients with epithelial ovarian cancer undergo postoperative systemic chemotherapy. 2

• For patients with stage II through IV disease, 6 to 8 cycles of chemotherapy are recommended. 2
• Intraperitoneal chemotherapy is recommended for patients with stage III, optimally debulked (< 1 cm residual) disease based on randomized controlled trials (category 1). 2
• The combination of intravenous paclitaxel plus carboplatin (category 1) is standard for patients with poor performance status or those unsuitable for intraperitoneal therapy. 2
• Survival was increased by 16 months after intraperitoneal therapy using cisplatin/paclitaxel compared with standard intravenous therapy (65.6 vs. 49.7 months; P = .03) in stage III cancer. 2

Hormone Receptor-Positive/HER2-Negative Breast Cancer: Selective Chemotherapy

For node-positive disease, all patients require chemotherapy regardless of hormone receptor status (Category 1 recommendation). 1

• For tumors ≤0.5 cm: Endocrine therapy alone is sufficient; chemotherapy provides minimal incremental benefit. 1
• For lymph node-negative, hormone receptor-positive breast cancer tumors greater than 1 cm, endocrine therapy with chemotherapy is recommended (category 1). 2
• Available data suggest that a discussion of omitting adjuvant chemotherapy in very young women (≤35 years at diagnosis) with low-risk ER+ disease is appropriate in highly selected cases with favorable clinical and pathological features including low gene expression profiles where available. 2

Important Caveat on Genomic Testing

• Commercially available gene expression signatures have not been widely studied in young women, and fewer data are available to establish their role in predicting the additional benefit of chemotherapy over endocrine therapy alone in HR+ breast cancer in this age group. 2
• Tamoxifen alone was given in the vast majority of premenopausal women enrolled in the trials exploring these tests. 2

Hodgkin Lymphoma: Fertility Considerations

Young women with Hodgkin lymphoma treated with chemotherapy are at risk of developing premature ovarian failure, irrespective of their age at the time of treatment (37% for those diagnosed between 9 and 29 years of age). 2

• The cumulative risk of premature ovarian failure after alkylating agent-based chemotherapy was 60% compared to only 3% or 6% after non-alkylating agent-based chemotherapy. 2
• Treatment with MOPP (mechlorethamine, vincristine, procarbazine, and prednisone)/ABV (doxorubicin, bleomycin, and vinblastine) significantly increased the risk of ovarian failure. 2
• The ABVD (doxorubicin, bleomycin, vinblastine, and dacarbazine) regimen has been shown to be less gonadotoxic, with a vast majority of patients regaining normal fertility after completion. 2

Key Clinical Pitfalls to Avoid

• Do not withhold chemotherapy from hormone receptor-positive patients solely based on ER-positive tumor status when other high-risk features are present. 2
• Young age by itself should not be an indication to prescribe a combination of cytotoxic agents. 2
• The indication for and the choice of adjuvant systemic treatment for invasive breast cancer should be driven by extent of disease and the biological characteristics of the tumor, not age alone. 2
• For the time being, the type of systemic treatment of early breast cancer is independent of BRCA or any other constitutional genetic status. 2