Implementation of a Percutaneous Core Needle Biopsy Training Program: Results from the University of Michigan-Komfo Anokye Teaching Hospital Breast Cancer Research Partnership

Abstract

Purpose

To describe a training program in percutaneous core needle biopsies implemented in conjunction with a breast cancer research collaboration between the University of Michigan (UM) and the Komfo Anokye Teaching Hospital (KATH) in Kumasi, Ghana.

Methods

In July 2008 a Ghana-based training program for the performance of core needle biopsies was jointly coordinated by the UM and KATH principal investigators (LAN and BA). This course required less than one week for implementation.

Results

Following the training course (July 2008 through to August 2009), 82 core needle biopsies of breast masses were performed at KATH. Of these, 56 had tissue specimens available for review at UM for comparison with KATH primary pathology reports. Forty-six of the 56 UM-reviewed cases (82%) had a KATH diagnosis of breast cancer; UM pathology review was in agreement with the cancer diagnosis in all 46 cases (100%). Ten of the 56 UM-reviewed cases (18%) had a KATH diagnosis of benign fibroadenoma/fibrocystic breast tissue; UM review was concordant in all ten cases (100% concordance for benign lesions). For the remaining 26 procedures we were unable to retrieve either the KATH pathology report or tissue blocks for UM review.

Discussion

The design and implementation of appropriate diagnostic biopsy programs is important for the delivery of quality, efficient breast cancer care in developing nations. This study demonstrates a successful one-week training program in percutaneous core needle biopsy for a multidisciplinary group of physicians. Further work is needed for similar programs to accurately identify and classify breast cancer internationally.

Introduction

The advantages of percutaneous core needle biopsies in evaluating breast abnormalities are well-documented. For lesions that are clinically consistent with benign abnormalities such as fibroadenoma, surgical interventions may be avoided, and for clinically-suspicious lesions, a needle biopsy is an efficient strategy for establishing a breast cancer diagnosis non-operatively. In the latter scenario, the diagnostic needle biopsy will then permit the patient and physician to proceed with planning of definitive breast and axillary staging surgery within a single initial operative experience. Furthermore, diagnostic needle biopsies prior to attempted breast conserving surgery have been shown to improve success rates with margin negativity and smaller-volume lumpectomies.^1,2 The percutaneous core needle biopsy as a breast evaluation strategy can be particularly valuable and effective in facilities that have a high prevalence of advanced-stage breast cancer, such as those located in underdeveloped nations. The bulky breast tumor is more likely to have a diagnostic needle biopsy, with minimal risk of sampling error. Facilities that have limited financial resources will also benefit from implementing a rapid, office or clinic-based biopsy maneuver that promotes more efficient utilization of operating room resources. Lastly, the healthcare of medically-underserved patients in underdeveloped countries is enhanced by opportunities to streamline clinic visits and cancer treatment planning. The present study describes the impact of a training program in percutaneous core needle biopsies implemented in conjunction with a breast cancer research collaboration between the University of Michigan and the Komfo Anokye Teaching Hospital in Kumasi, Ghana.

Methods

The University of Michigan (UM) has collaborated with the Komfo Anokye Teaching Hospital (KATH) in Kumasi, Ghana for the study of breast cancer in women with African ancestry as part of an IRB-approved program since June 2006. When this partnership was initiated, the primary definitive diagnostic intervention for women evaluated at KATH involved surgical incisional or excisional biopsies. In July 2008 a training program for the performance of core needle biopsies was jointly coordinated by the UM and KATH principal investigators (LAN and BA) for this research program. Participants included KATH medical staff involved with clinical care of breast patients; KATH pathology technicians; and KATH Breast clinic nursing staff. The program involved a didactic session followed by observation of core needle biopsies performed by an experienced surgical breast oncologist (LAN) and culminating with the hands-on performance of core needle biopsies by the KATH medical staff on KATH breast clinic patients after obtaining informed consent. The entire training course required less than one week for implementation. The KATH team (led by BA) identified seven patients with highly-suspicious, palpable breast abnormalities for participation. These cases were all discussed in the KATH multidisciplinary tumor board meeting, which was attended by members of the surgery service, pathology, medical oncology, and radiation oncology. The UM PI (LAN) provided the didactic discussion regarding the advantages and technique of percutaneous core needle biopsy during one of the KATH breast clinic sessions, as well as during this multidisciplinary tumor board meeting. The observational and hands-on biopsy program was then conducted in the KATH Breast Clinic facility. The UM PI (LAN) performed the percutaneous core needle biopsies on the initial patient, and the KATH participants as well as the UM PI performed the core needle biopsies on the remaining six patients, supervised by the UM PI. A minimum of three core needle passes were performed on each of the six patients, to maximize tissue yield and minimize sampling error.

We report herein the patterns of breast biopsies and pathology results at KATH after the implementation of this training program. All of the core needle biopsies at KATH (during and following the training session) were performed on palpable breast masses using 14-16 guage spring-loaded core needle biopsy devices featuring a 10-20 cm throw/core extraction length. A selection of these biopsy materials obtained via core biopsies and via surgical biopsies was evaluated by dedicated breast pathologists at UM in an effort to assess for reporting concordance. Additional histologic features and molecular marker features were evaluated by the University of Michigan team, as immunohistochemistry technology for estrogen receptor (ER); progesterone receptor (PR) and HER2/neu markers is not currently available at KATH. Details regarding the study of these markers is reported in the context of another report³.

Results

Following the core needle biopsy training course (July 2008 through to August 2009), 82 core needle biopsies of breast masses were performed at KATH. There were no cases of significant hematoma (requiring evacuation) or major infections (requiring hospitalization or intravenous antibiotics) complicating any of these procedures. A median of three (range, 2-5) core specimen passes were performed per patient.

Of the total sample, 56 had tissue specimens available for review at the University of Michigan for comparison with KATH primary pathology reports. Forty-six of the 56 UM-reviewed cases (82%) had a KATH diagnosis of breast cancer, and the UM pathology review was in agreement with the cancer diagnosis in all 46 cases (100%). Clinicopathologic features for the cancer cases (as per the University of Michigan pathology review) are shown in Table 1. Approximately two-thirds were invasive ductal carcinomas and 80% were grade 3 lesions. Seventy-six per cent of the cancers were ER-negative and two-thirds were negative for ER, PR, and Her2/neu (triple-negative).

Table 1.

Clinicopathologic features of the Ghanaian breast cancer patients diagnosed by percutaneous core needle biopsy.

Feature	Ghanaian Cancer Cases (n=46)
Median Age (range)	45 years (25-76)
Median Tumor Size (range)	4 cm (2-7)
No. Cases with Invasive Ductal Histology (%)	30 (65%)
No. Grade 3 Tumors	37 (80%)
No. Estrogen Receptor Negative Tumors (%)	35 (76%)
No. Triple-Negative Tumors (ER, PR, and HER2/neu-negative)	30 (64%)

Ten of the 56 UM-reviewed cases (18%) had a KATH diagnosis of benign fibroadenoma/fibrocystic breast tissue and the UM review was concordant in all ten cases (100% concordance for benign lesions).

For the remaining 26 core needle biopsy procedures we were unable to retrieve either the KATH pathology report or tissue blocks for UM review. The limited financial resources at KATH precludes the maintenance of a formal tumor registry with cancer case ascertainment and data extraction. Inconsistencies in medical record identifiers therefore resulted in these several cases where tumor blocks and medical record information could not be definitively and reliably matched.

Discussion

The twenty-first century is an era where the appropriate biopsy maneuver for a breast cancer patient is critical for planning optimal and comprehensive treatment. An initial diagnostic needle biopsy is rapid and cost-efficient (compared to surgical diagnostic biopsy), and since measureable disease will remain following utilization of this procedure, it preserves the option of neoadjuvant systemic therapy for selected patients. Core needle biopsies are generally preferred over fine needle aspiration biopsies because of the generally lower sampling error associated with the former and because of the larger volume of tissue retrieved, making it possible for the pathologist to document invasive versus in situ disease and to grade the tumor accurately. Immunohistochemical assays for the three standard molecular markers utilized in breast cancer (estrogen receptor; progesterone receptor; and HER2/neu) are critical for determining appropriate adjuvant systemic therapy options and these markers are more reliably-obtained with core needle biopsies as well. Although immunohistochemistry can indeed be performed on cytology specimens, it is impossible to determine whether the evaluated markers are from the invasive tumor cells or the in situ component and it is the marker panel from the invasive cancer that determines treatment recommendations. Patients with tumors that are positive for the estrogen receptor and/or the progesterone receptor will be candidates for endocrine therapy, and patients with tumors that overexpress HER2/neu will be candidates for traztusamab therapy. Lastly, node-negative and estrogen receptor positive breast cancer patients will be eligible for genetic profiling to determine their 21-gene recurrence score (OncotypeDx), and this information may also guide decisions regarding adjuvant chemotherapy in addition to endocrine therapy.^4-6

Furthermore, it is now well-established that breast cancer is a disease comprised of several different tumor subtypes that are characterized by varying degrees of malignant potential. The molecular marker panel can provide a surrogate classification schema for identifying these subtypes. For example, the basal breast cancer subtype is generally perceived as being a particularly aggressive and virulent pattern, and most of these tumors are identified as the “triple-negative” breast cancers that are negative for expression of the estrogen, progesterone, and HER2/neu markers. The study of breast cancer disparities has led to an increased appreciation for race-ethnicity-associated variation in prevalence of breast cancer subtypes. Most notably, women with African ancestry (African as well as African-American) have a significantly higher frequency of estrogen receptor-negative and triple-negative/basal breast cancer subtypes^7-11. The molecular marker patterns of this Ghanaian breast cancer subset were consistent with our findings from a larger comparative analysis involving Ghanaian, African American, and White American cases.³ Studies of the breast cancer burden among the developing nations of Africa will therefore become increasingly important as we seek to understand the genetics of basal breast tumors, and as we try to identify markers that may be useful for prevention and/or treatment. Industrialized and developed nations therefore have an obligation to share best practices and improved diagnostic technology with developing nations because it is “the right thing to do” and also because these partnerships can promote valuable research opportunities regarding the pathogenesis of high-risk breast cancer.

For these reasons, we hypothesized that a training program in percutaneous core needle biopsies would be a valuable system for the breast oncology program at KATH in Kumasi, Ghana. Ghana is located on the western, sub-Saharan coast of Africa. It has been an independent country with a democratically-elected government and English as its official language, since 1957. It has an estimated population of 18,412,247 (females-51%, males 49), resulting in an overall population density of 201 persons per square mile. The most densely populated parts of the country are the coastal areas, the Ashanti region, and the two principal cities, Accra and Kumasi. KATH is located in Kumasi, which is the capital city for the Ashanti region of Ghana and has a population of more than one-and-a-half million. Ghana is widely-acknowledged to be one of the most economically and politically stable countries in Africa, however with an unemployment rate of 20% and nearly one-third of its population living below the international poverty line of US$1.25 per day, it is clearly underdeveloped in comparison to more affluent western populations. The Ghanaian population is clearly medically underserved, with approximately 15 physicians and 93 nurses per 100,000 persons, and life expectancy 59 years for men and 60 years for women^12,13.

Globocan International¹⁴ estimates breast cancer incidence and mortality rates to be approximately 24.8 and 11.3 per 100,000 population respectively, however the imprecision of these rates must be emphasized because of suboptimal data collection regarding cancer cases in undeveloped countries where tumor registries are non-existent. The limited financial resources at KATH precludes the maintenance of a centralized hospital-based cancer registry, however it is estimated that approximately 250 newly-diagnosed breast cancer patients are evaluated annually, and that more than three-quarters of these patients have locally advanced disease. Because mammographic screening is not widely or uniformly available to the Ghanaian female population, the vast majority of breast cancer patients seen at KATH present with palpable, clinically overt disease. Percutaneous, free-hand needle biopsy represents the only alternative to surgical biopsy, because image-guidance via mammography or breast ultrasound is not widely available. This procedure spares the women from having to return to the hospital for a diagnostic surgical biopsy, and it supports more efficient utilization of the surgical suite services. Lastly, the collaborative relationship that grew as a consequence of conducting this training program strengthened the ongoing international breast cancer research program that currently underway between the University of Michigan and the Komfo Anoyke Teaching Hospital.

A major limitation of our study is the fact that we do not have follow-up information on the benign needle biopsies, and so we cannot assess the false-negative rate. However the concept of sampling error associated with needle biopsies was strongly emphasized in the course of our training program, so that all participants were aware of the need to pursue additional surgical biopsy efforts if the needle biopsy result was discordant with the clinical impression.

As research involving breast cancer disparities expands in the direction of international work involving developing nations, it will become increasingly important to implement appropriate diagnostic biopsy programs. These programs must above all serve the purpose of accurately identifying and classifying a breast cancer, and they should also be suitable for tissue acquisition that can be banked for future diagnostic, treatment, and research needs¹⁵. Our study demonstrated that implementation of a one-week training program in percutaneous core needle biopsy among a multidisciplinary group of physicians was well-received and effective.