The Benefits of a "Complete Response"

For many cancer sites, the use of neoadjuvant radiation and/or chemotherapy is becoming a standard strategy. One of the greatest benefits is the opportunity to achieve a complete clinical or pathological response prior to surgical resection.

In the management of pancreatic adenocarcinoma, achieving a pathologic complete response was associated with a twofold higher 5-year overall survival rate among patients with localized pancreatic adenocarcinoma who underwent preoperative chemoradiotherapy (CRT) and resection. Several factors, including treatment type and tumor features, influenced the outcomes.

In a current analysis, researchers investigated the incidence and factors associated with pathologic complete response after preoperative CRT among 1,758 patients (mean age, 64 years; 50% men) with localized pancreatic adenocarcinoma who underwent resection after two or more cycles of chemotherapy (with or without radiotherapy). Pathologic complete response was defined as the absence of vital tumor cells in the patient's sampled pancreas specimen after resection.

• Researchers found that the rate of pathologic complete response was 4.8% in patients who received CRT before pancreatic cancer resection.
• Having a pathologic complete response was associated with a 54% lower risk for death. At 5 years, the overall survival rate was 63% in patients with a pathologic complete response vs. 30% in patients without one.
• More patients who received preoperative modified FOLFIRINOX achieved a pathologic complete response (58.8% vs 44.7%). Other factors associated with pathologic complete response included tumors located in the pancreatic head, tumors > 40 mm at diagnosis, partial or complete radiologic response, and normal(ized) serum carbohydrate antigen, CA 19-9, after preoperative therapy.

These findings again show the benefit of complete data in patient abstracts that reflect the use of neoadjuvant treatment. The combination of data from multiple institutions is also important.

The De-escalation of Breast Cancer Therapy

One of the great challenges in modern cancer management is to limit or discontinue traditional therapies that have not proven beneficial in certain populations of patients. Adjuvant radiotherapy is prescribed after breast-conserving surgery to reduce the risk of local recurrence. However, radiotherapy is inconvenient, costly, and associated with both short-term and long-term side effects.

Clinicopathologic factors alone are of limited use in the identification of women at low risk for local recurrence in whom radiotherapy can be omitted. Molecularly defined intrinsic subtypes of breast cancer can provide additional prognostic information.

A prospective cohort study reports results in 500 women who were at least 55 years of age, had undergone breast-conserving surgery for T1N0 (tumor size <2 cm and node negative), grade 1 or 2, luminal A–subtype breast cancer (defined as estrogen receptor positivity of ≥1%, progesterone receptor positivity of >20%, negative human epidermal growth factor receptor 2, and Ki67 index of ≤13.25%), and had received adjuvant endocrine therapy. Among women who were at least 55 years of age and had T1N0, grade 1 or 2, luminal A breast cancer that were treated with breast-conserving surgery and endocrine therapy alone, the incidence of local recurrence at 5 years was low with the omission of radiotherapy.

Radiotherapy of the breast is commonly administered after breast-conserving surgery to reduce the risk of local recurrence and thereby avoid mastectomy. However, radiotherapy is inconvenient for patients, involving 3 to 6 weeks of daily treatments, and is costly. It is also associated with considerable short-term side effects, such as fatigue, skin irritation, and breast swelling, and long-term side effects, such as skin telangiectasia, breast pain, induration, and retraction, that can adversely affect cosmesis and quality of life. Rarely, breast radiotherapy can cause second cancers and ischemic cardiac disease.

The use of Ki67 identifies a potentially useful marker, although not currently captured as an element of TNM staging of breast cancer. It is important to capture these types of markers in our cancer registries for many types of cancers to help in identifying instances in which traditional therapies can be abandoned.

Male Breast Cancer

Despite the overwhelming number of breast cancer cases in women, the importance of male breast cancer collected by our cancer registries remains an important topic. One important question would be: What is the breast cancer–specific mortality (BCSM) risk over 20 years in men with stage I to III hormone receptor–positive breast cancer?

In women with hormone receptor–positive (HR⁺) breast cancer, the risk of distant recurrence and death persists for at least 20 years from diagnosis. The risk of late mortality in men with HR⁺ breast cancer has previously not been reported. An observational cohort study was conducted of men diagnosed with HR⁺ breast cancer from 1990 to 2008, using population-based data from the Surveillance, Epidemiology, and End Results program. Men diagnosed with stage I to III HR⁺ breast cancer were included in the analysis. The cumulative 20-year risk of BCSM was 12.4% for Stage I, 26.2% for Stage II, and 46.0% for Stage III. The findings of this study suggest that the risk of BCSM at 20 years is high in men with hormone receptor–positive breast cancer.

What are the factors associated with late BCSM? Among patients who survived 5 years from diagnosis, the adjusted BCSM risk was higher for those younger than 50 years versus older than 64 years, those with Grade II or III/IV versus Grade I tumors, and Stage II or III versus Stage I disease. The findings of this study suggest that, in men with Stage I to III HR⁺ breast cancer, the risk of BCSM persists for at least 20 years, and depends on traditional clinicopathologic factors, such as age, tumor stage, and tumor grade.

Among men with higher stages of the disease, the kinetics of the BCSM risk appear different from the risk that has been reported in women.