Breast biopsy techniques in a global setting-clinical practice review.

Breast cancer is a disease of global concern, regardless of economic status. A significant disparity in breast cancer care between low- and high-income countries is not unexpected, but consideration can be given to particular aspects of therapy to allow as much equitability as possible. One of these aspects involves biopsy of breast lesions. With available resources, management in developed countries focuses on dealing with screening and image-detected lesions. In such circumstances, advanced percutaneous biopsy techniques are utilized liberally. However, where resources are less forthcoming for mammographic screening, women frequently present with symptomatic, palpable and larger tumours. This scenario behooves the clinician to modify treatment approaches and yet use cost-effective management strategies. It is essential that thought is applied to breast biopsy technique used where there is cost-consciousness as it significantly influences subsequent therapy. Less expensive strategies like fine needle aspiration cytology (FNAC) and core needle biopsy (CNB), when performed with particular attention to technique, handling, transportation and preparation of biopsy specimens allows a high level of accuracy and provides adequate information for the next steps in treatment. This mini-review discusses the variation in biopsy approaches among lower and higher income areas and offers suggestions for appropriate breast biopsy strategies in resource-limited countries.

The Impact of Margin Status on Breast Conservation Rates.

BACKGROUND: Contemporary data indicate that breast conservation treatment (BCT) results in superior survival outcomes compared with mastectomy. However, positive margins after lumpectomy have implications for local control, and re-excisions are recommended to achieve negative margins. The need for reoperations after an initial attempt at BCT is associated with higher chance of conversion to mastectomy. Achieving negative margins at the first therapeutic surgical procedure is therefore critical to optimise BCT rates and survival outcomes. METHODS: A compilation of scientific reports on BCT, margin status, rates of reoperation, and the impact on BCT rates was reviewed. Re-excision rates after initial lumpectomy is variable to a staggering degree and reported to be between 0 and 100%. High reoperation rates (ROR) are associated with higher likelihood of conversion to mastectomy, which may not confer favourable treatment outcomes. Although widely agreed that decreasing ROR is a desirable objective, there is controversy regarding the need for its urgent implementation as a quality metric. Critics of this cite challenges related to how this can be achieved and its attendant ramifications. On the other hand, without the appropriate incentive for quality improvement of surgical treatment of breast cancer, patients may be subject to poorer overall outcomes. DISCUSSION: Techniques and approaches are discussed in this article to enable a reduction in positive margin status, and therefore ROR. The rationale for achieving ROR of 10-20% are explicated, as well as the impact this would have on BCT rates, which translates to better survival outcomes for women with breast cancer.

Addressing the paradox of increasing mastectomy rates in an era of de-escalation of therapy: Communication strategies.

Breast conservation therapy (BCT) was established as the preferred modality of surgical treatment for early stage breast cancer in the early 1990's. Yet, rising mastectomy rates have been observed over the last decade. This increase is a cause for concern as recent large population-based studies have consistently reported improved breast cancer-specific survival and local control rates with BCT, in comparison with mastectomy. There is a pressing need to formulate strategies to effectively inform both patients and practitioners about current data, in the hope of reversing rising mastectomy rates to optimise survival outcomes. Based on the available evidence relating to the motivators for a mastectomy, a format for presenting data to bridge the existing knowledge deficit for effective patient counselling is proposed in this review.

The Intersection of National Immigration and Healthcare Policy.

Immigration policy and health care policy remain principal undertakings of the federal government. The two have recently been pursued independently in the judicial and legislative arenas. Unbeknownst to many policymakers, however, national immigration policy and health care policy are linked in ways that, if unattended, could undermine the well-being of a significant portion of the US population, specifically medically underserved rural and urban populations. Using current data from a workforce report of the Association of American Colleges and the published literature, we demonstrate the significant impact that contemporary immigration policy directives may have on the number and distribution of international medical graduates who currently provide-and by the year 2025 will provide-a significant portion of primary health care in the United States, especially in underserved small urban and rural communities.

Approach to management of giant basal cell carcinomas.

Basal cell carcinoma (BCC) is a common nonmelanoma skin cancer with increasing incidence in the United States and worldwide. It is strongly linked to UV radiation exposure and typically is slow growing. Malignancy in BCCs is due to local growth and invasion rather than metastasis, and the prognosis is generally favorable. We report the case of a 60-year-old man with a large, locally destructive giant BCC on the right side of the upper back that was successfully treated via complete surgical excision (SE) and did not recur in the subsequent 36 months. We review the indications, evidence, advantages, and disadvantages associated with multiple surgical and nonsurgical treatment modalities available for the management of giant BCCs.

Adjunct primer for the use of national comprehensive cancer network guidelines for the surgical management of cutaneous malignant melanoma patients.

Recently, a Surveillance Epidemiology and End Results (SEER) survey of melanoma patterns of care by the Mayo Clinic, Scottsdale showed remarkable deviations from best practice patterns throughout the country. The study, which analyzed the SEER records of 35,126 stage I to III cutaneous malignant melanoma patients treated from 2004 to 2006, showed that adherence to National Comprehensive Cancer Network (NCCN) therapeutic resection margins occurred in less than 36% of patients. Similarly, considerable variation in the quality of melanoma care in the United States when assessed using 26 quality indicators drawn by a panel of melanoma experts was independently reported. These observations underscore the significant lack of adherence to published best practice patterns reflected by the NCCN guidelines. The untoward effects of these variations in practice pattern can have an inordinate impact on the survival of melanoma patients in whom long term outcomes are affected by the adequacy of surgical management. Thin malignant melanoma is curable; however, thick or node positive melanoma is often incurable. This outcome is determined not only by the stage at presentation but by the use of best practice patterns as reflected in current NCCN cutaneous melanoma practice guidelines.

High resolution intra-operative two-dimensional specimen mammography and its impact on second operation for re-excision of positive margins at final pathology after breast conservation surgery.

BACKGROUND: In the United States, about 50% to 66% of women undergoing breast conservation surgery for cancer undergo subsequent mastectomy for positive margins on initial lumpectomy. This is despite the fact that screening mammography has resulted in a decrease in the size of newly diagnosed breast cancer to <2 cm. METHODS: A retrospective review of 128 patients who underwent breast conservation surgery for early breast cancer was performed using intraoperative 2-dimensional Faxitron high-resolution specimen mammography without specimen compression as the only margin assessment technique. Of these, 29 patients had histories of lumpectomy with positive margins. RESULTS: A total of 131 procedures were performed. Margins were histologically clear at initial breast conservation surgery in 84.3% of patients who underwent primary lumpectomy. Subsequent reexcision for positive margins was required in 14.7% of patients. Two-dimensional Faxitron mammographically guided intraoperative reexcision cleared the margins in 95.8% of patients (23 of 24) who would have otherwise required subsequent reexcision. CONCLUSIONS: Intraoperative 2-dimensional Faxitron high-resolution specimen mammography can decrease rates of margin positivity and has the potential to diminish the number of subsequent undesired mastectomies for positive margins.

Current Controversies on the Use of Magnetic Resonance Imaging in the Management of Breast Cancer.

The use of magnetic resonance imaging in the management of unselected female populations with early stage breast cancer has increased markedly over the past decade. Parallel to this trend many have observed an increased use of mastectomy over breast conservation due to concerns raised by the use of MRI. Similar concerns have led to the use of contra-lateral prophylactic mastectomy in patient populations not tested for potential genetic predisposition. These trends are difficult to understand as they divert from well established clinical paradigms which have been the result of widely accepted clinical research trials with more than three decades of clinical follow up. These trials have asserted that breast conserving surgery remains the accepted approach over mastectomy for the care of the patient with sporadic early stage breast cancer.

Expression of leukemia/lymphoma-related factor (LRF/POKEMON) in human breast carcinoma and other cancers.

The POK family of proteins plays an important role in not only embryonic development and cell differentiation, but also in oncogenesis. Leukemia/lymphoma-related factor (LRF) belongs to the POK family of transcriptional repressors and is also known as POK erythroid myeloid ontogenic factor (POKEMON), which binds to short transcripts of HIV-1 (FBI-1) and TTF-1 interacting peptide (TIP21). Its oncogenic role is known only in lymphoma, non-small cell lung carcinoma, and malignant gliomas. The functional expression of LRF in human breast carcinoma has not yet been confirmed. The aim of this study was to investigate and compare the expression of LRF in human breast cancer tissues and other human tumors. The expression of LRF mRNA transcripts and protein was observed in twenty human benign and malignant breast biopsy tissues. Expression of LRF was observed in several formalin-fixed tissues by immunohistochemistry and immunofluorescence. All malignant breast tissues expressed mRNA transcripts and protein for LRF. However, 40% and 15% benign breast biopsy tissues expressed LRF mRNA transcripts and protein, respectively. The overall expression of LRF mRNA transcripts and total protein was significantly more in malignant breast tissues than the benign breast tissues. LRF expression was also observed in the nuclei of human colon, renal, lung, hepatocellular carcinomas and thymoma tumor cells. In general, a significantly higher expression of LRF was seen in malignant tissues than in the corresponding benign or normal tissue. Further studies are warranted to determine the malignant role of LRF in human breast carcinoma.

Targeted tailored management of the breast cancer patient at risk for harboring a germline mutation-current trends affecting the selection of patients considering surgical prophylaxis for breast cancer.

Recent reports have documented the increasing use of mastectomy in women with breast cancer otherwise amenable to breast conservation. Similarly, other reports document an increase in the number of women undergoing contra-lateral prophylactic mastectomy for a single unilateral breast cancer. These trends are abetted by increasing use of MRI, inadequate risk counseling, and patient fear. Adequate and reliable risk assessment and genetic counseling are indispensable for the appropriate and personalized treatment of these individuals. In all of these instances, such counseling should be instituted well before the patients are submitted to any surgical intervention. An algorithm is presented which permits the orderly selection of patients who may benefit from such aggressive surgical intervention.

Hereditary diffuse gastric cancer: prophylactic surgical oncology implications.

Hereditary diffuse gastric cancer (HDGC) is an autosomal dominantly inherited syndrome attributed to mutations of the E-cadherin gene, CDH1. There is no proven effective screening for early HDGC, and symptomatic disease is almost universally fatal. The only available effective option for CDH1 carriers is prophylactic total gastrectomy, but the variable age of onset of HDGC and the reduced penetrance (about 70%) of the CDHI gene further complicate patients' decision making.

Genetic counseling and clinical management of newly diagnosed breast cancer patients at genetic risk for BRCA germline mutations: perspective of a surgical oncologist.

Women with a family history of breast cancer who are diagnosed with breast cancer are often counseled to undergo prophylactic mastectomy as part of their treatment for breast cancer. The majority of such individuals make these decisions in haste and without appropriate genetic counseling or testing. Most of them when tested for BRCA or other established mutations find that they are not mutation carriers. In retrospect, this realization leads many to question the wisdom of their prophylactic surgery which is often associated with complications and quality of life problems which they never envisioned. We have designed an algorithm for the management of these patients which minimizes these lifelong problems.

Hereditary breast cancer: part II. Management of hereditary breast cancer: implications of molecular genetics and pathology.

Management of patients at high risk for hereditary breast cancer (HBC) must critically assess its phenotypic and genotypic heterogeneity, particularly evidenced by the varying spectra of cancer sites that are integral to the respective HBC syndromes. Targeted management must consider their biology, pathology, and molecular genetics, all in concert with their respective carcinogenic pathways, as they may differ significantly from one breast cancer syndrome to the next. A striking example of management differences pertains to BRCA1 and BRCA2 mutation-positive breast cancers wherein those with BRCA1 mutations are frequently estrogen receptor (ER)-negative in contrast to BRCA2 mutations which are more frequently ER-positive; therein, significant differences exist with respect to anti-estrogen therapy which will be more amenable to BRCA2 versus BRCA1 mutation carriers manifesting breast cancer. In turn, tumors that are negative for ER, PR, and Her2-neu, often referred to as "triple negative" tumors, may also harbor a unique basal-like gene expression profile and are characterized by poor prognosis wherein endocrine and/or Her2-neu-targeted therapies are not effective treatment options. A further confounder pertains to the lifetime risk for ovarian cancer, which differs strikingly between BRCA1 mutation carriers, who show a 40-60% lifetime risk, and their BRCA2 counterparts, who carry a lifetime risk of approximately 12-15% for ovarian cancer. It is clear that as we learn more about the biology and the molecular aspects of hereditary forms of breast cancer, it will be compelling for the clinician to integrate this knowledge with pharmacologic, radiologic, and surgical treatment options for these high-risk patients.

Hereditary breast cancer: part I. Diagnosing hereditary breast cancer syndromes.

Hereditary breast cancer (HBC) accounts for as much as 10% of the total BC burden. Most of these cases will be found to be due to a BRCA germline mutation. An estimated additional 15-20% of those affected with BC will have one or more first- and/or second-degree relatives with BC. Therefore, when these numbers are combined, familial BC risk accounts for approximately 20-25% of the total BC burden. However, because of the often limited information on family history in the etiologic assessment of BC, this may be an underestimate. Confounding factors include its phenotypic and genotypic heterogeneity, given the association of HBC with a plethora of differing cancer syndromes. Its most common occurrence is its association with ovarian cancer in the so-called hereditary breast-ovarian cancer syndrome due to BRCA1 and BRCA2 mutations. More rarely, it occurs in the Li-Fraumeni syndrome, caused by a p53 germline mutation, in which markedly early-onset BC is found in association with brain tumors, sarcomas, leukemia, lymphoma, malignant melanoma, and adrenal cortical carcinoma. Importantly, the age-adjusted incidence of BC in women in the United States fell sharply, by 6.7%, in 2003, when compared with the rate identified in 2002. We postulate that increasing knowledge about the genetics of BC may have partially contributed to the identification of high-risk patients who thereby may have benefited significantly from early diagnosis.

Giant pelvic solitary fibrous tumor obstructing intestinal and urinary tract: a case report and literature review.

We are reporting a giant pelvic neoplasm, a rare solitary fibrous tumor that presented with a large bowel obstruction and bilateral ureteral obstruction because of its size and location. Preoperative diagnosis required complex pathological studies to exclude a high-grade sarcoma suspected clinically. Complete resection was required for resolution of obstructive symptoms. Prognosis for solitary fibrous tumors is usually good after complete resection. Recurrence and metastasis may be related to rare aggressive histological features, including nuclear atypia, hypercellularity, greater than four mitoses/10 high power fields, and necrosis. Because histology is not always a reliable predictor of prognosis, careful long-term follow-up is necessary for this tumor. Solitary fibrous tumors (SFTs) are rare spindle cell neoplasms most likely arising from mesenchymal cells. SFTs were originally described in the pleura, the most common site for this tumor; however, extrathoracic SFTs are seemingly diagnosed with increased frequency. We report a case of a giant pelvic SFT that required complicated clinical management.