Thomas A. Buchholz

Classifying local disease recurrences after breast conservation therapy based on location and histology: New primary tumors have more favorable outcomes than true local disease recurrences

To distinguish true local recurrences (TR) from new primary tumors (NP) and to assess whether this distinction has prognostic value in patients who develop ipsilateral breast tumor recurrences (IBTR) after breast‐conserving surgery and radiotherapy.

Positive surgical margins and ipsilateral breast tumor recurrence predict disease-specific survival after breast-conserving therapy

Meric et al. recently concluded that currently available data are not sufficient to determine conclusively whether distant metastases are caused by the development of ipsilateral breast tumor recurrence (IBTR). The authors of at least four randomized, prospective trials do not agree. For example, the National Surgical Adjuvant Breast and Bowel Project (NSABP) concluded that local recurrence is a marker for risk (and not a cause) of distant metastases. Meric et al. also concluded that it would be difficult to argue biologically that malignant cells in the primary tumor could metastasize and affect survival while arguing that malignant cells in the recurrent tumor could not. I have offered this explanation. It is likely that cancer cells begin to circulate when a tumor is very small. Cells shed from a small tumor may succumb to a variety of host defense factors—mechanical, biochemical, immunologic, etc. After breast-conserving surgery, cancer may recur locally. (Here, I prefer the term local persistence.) Patients who survive their first cancer without developing distant metastases may be expected to survive the recurrence of a similar volume of tumor, because the host defense factors that killed tumor cells from the primary tumor can be expected to kill tumor cells shed from the recurrence (persistence). Local recurrence after radical surgery has always been an ominous event. It may represent the return of malignant cells from a distant organ to the site of surgery. Local recurrence also may occur after breast-conserving surgery. This is one reason why patients who develop IBTR have a poorer prognosis compared with patients who do not. In NSABP trial B-06, patients who developed local recurrence were 3.41 times as likely to also develop distant metastases. This is not evidence that IBTR is the cause of tumor spread. Investigators from the NSABP trial B-06 recently reported a marginally significant decrease in breast cancer deaths among women who received postoperative radiotherapy. This finding is fully compatible with the above hypothesis. The excess deaths in the unirradiated group may have occurred in women whose recurrences exceeded their primary tumors in terms of volume. I asked the NSABP for data on the size of tumor recurrences and was told that such data are not available. Meric et al. discussed the possible survival advantage associated with local control. They cited important studies that will help us fine-tune our understanding of this dilemma. However, the past 15 years have witnessed a dramatic change in our understanding of local recurrence. Local persistence seldom metastasizes in patients with the soft tissue sarcomas, rectal carcinoma, melanoma, and other solid tumors. Investigators at The University of Texas M. D. Anderson 2522

Breast conservation after neoadjuvant chemotherapy: A prognostic index for clinical decision-making

The appropriate selection criteria for breast‐conserving therapy (BCT) after neoadjuvant chemotherapy are poorly defined. The purpose of the current report was to develop a prognostic index to help refine selection criteria and to serve as a general framework for clinical decision‐making for patients treated by this multimodality approach.

Neoadjuvant chemotherapy for breast carcinoma: Multidisciplinary considerations of benefits and risks

The majority of patients with breast carcinoma receive chemotherapy as a component of multimodality treatment. Over the past decade, it has become increasingly more common to deliver chemotherapy first, but this has raised new questions within all disciplines of cancer management.

Improving local control with breast-conserving therapy: a 27-year single-institution experience.

The risk of ipsilateral breast tumor recurrence (IBTR) after breast‐conserving therapy (BCT) is associated with treatment and tumor‐related variables, such as surgical margin status and the use of systemic therapy, and these variables have changed over time. Correspondingly, the authors of the current study hypothesized that the contemporary multidisciplinary management of breast carcinoma would lead to an improvement in IBTR rates after BCT.

Prognostic significance of phosphorylated P38 mitogen‐activated protein kinase and HER‐2 expression in lymph node‐positive breast carcinoma

Chemotherapy‐induced p38 mitogen‐activated protein kinase (MAPK) phosphorylation reportedly leads to increased apoptosis in breast carcinoma cells. The goals of the current study were to assess the incidence of activated phosphorylated p38 MAPK (P‐p38) expression in invasive breast carcinoma, correlate expression of P‐p38 MAPK with HER‐2, and estimate the prognostic value of this marker in patients with lymph node‐positive breast carcinoma treated with adjuvant chemotherapy.

Clinical outcome of patients with lymph node-negative breast carcinoma who have sentinel lymph node micrometastases detected by immunohistochemistry

The ideal pathologic assessment of sentinel lymph nodes (SLNs) in patients with breast carcinoma remains controversial. The authors evaluated how detailed assessment of SLNs using immunohistochemistry (IHC) and serial sectioning would affect treatment decisions and outcomes in patients with breast carcinoma who had negative SLNs on standard hematoxylin and eosin staining.

Assessment of histologic features and expression of biomarkers in predicting pathologic response to anthracycline‐based neoadjuvant chemotherapy in patients with breast carcinoma

There is significant variability in the response of tumors to neoadjuvant chemotherapy, and the underlying mechanism for this variability is unknown. In this study, the authors investigated the roles of tumor nuclear grade, mitotic activity, and biomarker expression profiles in predicting the pathologic response of breast tumors to preoperative chemotherapy.

A case–control study of unilateral and bilateral breast carcinoma patients

Women with unilateral breast carcinoma are at increased risk for developing contralateral disease. The clinical significance of bilateral breast carcinoma has not been fully defined, and the subset of patients who may benefit from medical or surgical risk‐reduction intervention has not yet been characterized. The purpose of this study was to evaluate risk factors and outcomes for bilateral breast carcinoma.

Breast Conservation Therapy as a Treatment Option for the Elderly The M. D. Anderson Experience

Although almost half of all incidents of breast carcinoma occur in women age ≥ 65 years, not enough is known about appropriate care for patients in this age group. The objective of the current study was to evaluate the role of breast conservation therapy in the management of breast carcinoma in women age ≥ 65 years.