Michael Koretz

The impact of the 21-gene recurrence score assay on decision making about adjuvant chemotherapy in early-stage estrogen-receptor-positive breast cancer in an oncology practice with a unified treatment policy

BACKGROUND The 21-gene recurrence score (RS) assay has been validated in retrospective studies as prognostic of distant disease recurrence and predictive of the benefit of adjuvant chemotherapy in estrogen-receptor-positive breast cancer (BC). There is limited published data on the impact of the assay on clinical practice, particularly in the context of a single practice with a unified treatment policy. PATIENTS AND METHODS Between 2006 and 2009, RS was obtained on 135 patients in a single practice with a uniform treatment policy. Treatment recommendations before and after RS result were analyzed retrospectively. Pre-RS treatment recommendations were based on clinicopathological features and Adjuvant! Online (AO) calculated survival advantage. RS and AO survival advantage for adding chemotherapy were compared for each patient. RESULTS The distribution by risk group of RS was low- 49.6%, intermediate-37.8%, and high-12.6%. In 34 patients (25.2%, 95% confidence interval 17.9% to 32.5%), recommendation for chemotherapy was changed after obtaining assay result. Most changes (70.6%) were from chemotherapy to no chemotherapy. The RS correlated poorly with AO predictions. CONCLUSION The 21-gene assay, when applied in a consistent manner in early-stage BC, changes treatment recommendations in one-quarter of patients tested.

Abdominal wall pain in pregnant women caused by thoracic lateral cutaneous nerve entrapment

Three pregnant women presented with disabling lower abdominal wall pain unresponsive to conventional therapies. The striking similarities among the clinical signs and symptoms prompted a review of the literature and led to the suspicion of thoracic lateral cutaneous nerve entrapment, a syndrome reported in other conditions, including after surgery, but not during pregnancy. Treatment by nerve block with local anesthetics was rapidly and completely successful in relieving the symptoms.

Double seton—A new modified approach to high transsphincteric anal fistula

Despite the fact that complicated extrasphincteric anal fistulas have been recognized and treated for many years, there is still a lack of consensus among colorectal surgeons as to the optimum surgical approach. We have devised a modification of the seton technique, which we used in 23 patients without complications or recurrence.

Association between Bone Mineral Density and Incidence of Breast Cancer

Introduction Previous studies have suggested an inverse relationship between bone mineral density (BMD) and breast cancer incidence. The primary objective of this study was to assess whether BMD is associated with risk of subsequent breast cancer occurrence in the female population of southern Israel. Methods The electronic medical charts of women who underwent BMD at the Soroka Medical Center (SMC) between February 2003 and March 2011 were screened for subsequent breast cancer diagnoses. Women were divided by tertiles of BMD at 3 skeletal sites: lumbar spine (LS, L1–4), total hip (TH) and femoral neck (FN). The incidence of breast cancer was calculated. Results Of 15268 women who underwent BMD testing, 86 were subsequently diagnosed with breast cancer. Most women in the study were older than 50 years (94.2% and 92.7%, respectively; p = 0.597). Women who subsequently developed breast cancer had a higher mean body-mass index (BMI) (30.9±5.5 vs. 29.1±5.7 p = 0.004) and the mean BMD Z-score was significantly higher than in those without breast cancer for all 3 skeletal sites (LS: 0.36±1.58 vs. −0.12±1.42, p = 0.002; TH: 0.37±1.08 vs. 0.03±1.02, p = 0.002; FN: 0.04±0.99 vs. −0.18±0.94; p = 0.026). Women in the highest Z-score tertiles at the FN and TH had a higher chance of developing breast cancer compared to the lowest tertile; odds ratio of 2.15, 2.02, respectively (P = 0.004 and 0.01 respectively). No association was found between the BMD Z-score and the stage, histology, grade or survival from breast cancer. Conclusions This study provides additional support for an inverse association between BMD and the risk of breast cancer.

Role of Wire-guided Breast Biopsy for Diagnosis of Malignant Nonpalpable Mammographic Lesions

Abstract. Biopsies of mammographically detected nonpalpable lesions have resulted in increased numbers of diagnosed early breast malignancies. From June 1992 to September 1996 a total of 433 consecutive patients underwent 438 biopsies. The mean age was 55.7 years (range 30–82 years); 150 patients were younger than 50 years. Mammographic findings were classified as microcalcifications (C), masses (M), masses with microcalcifications (MC), architectural distortions (A), and stellate lesions (S). In 30 women two needles were placed to localize a lesion in the ipsilateral side and in 5 on the contralateral side. There were 182 (41.6%) biopsies performed for M, 144 (32.9%) for C, 78 (17.8%) for A, 25 (5.7%) for MC, and 9 (2.1%) for S. The overall malignancy rate was 34% (149/438). Thirty-four women (23%) who presented malignancy were younger than 50 years of age. From year to year, it increased from 27% during the first year to 51% during the fourth year. Altogether 100 (67%) patients had invasive carcinoma, 40 (27%) ductal carcinoma in situ (DCIS), 6 (4%) lobular carcinoma in situ, and 3 (2%) tubular carcinoma. Four patients had simultaneous bilateral palpable and nonpalpable carcinoma. Among the patients, 9 of 20 with previously operated breast carcinoma and 9 of 19 with other previous malignancies were found to have early breast carcinoma. The mammographic finding with high rates of malignancy were S 67%, MC 40%, M 34%, C 33%, and A 28%. A group of 11 of 110 (10%) patients had histologically proven axillary lymph node metastasis. Results from this large retrospective study of wire-guided localization biopsies showed a relatively high rate of malignancy (34%) and DCIS (27%).

Stage I breast cancer in a regional oncology practice in Israel 2002-2006: clinicopathologic features, risk estimation and planned therapy of 328 consecutive patients.

We present the clinicopathologic features and treatment plans of 328 consecutive stage I (T1N0M0) breast cancer patients seen at a regional medical center in Israel. Predicted 10-year mortality risk was calculated using the Adjuvant! Online website. The 21-gene recurrence score (RS) (OncotypeDx) was obtained on a minority of patients. Eighty-nine per cent of patients had estrogen receptor (ER) and/or progesterone receptor (PgR) positive tumors. In 43.3% of patients history of an invasive malignancy was reported in a first degree relative and in 15.5% specifically breast and/or ovarian cancer was reported. Chemotherapy was added to endocrine therapy in 59 ER/PgR positive patients, decreasing predicted 10-year mortality risk by a median of 1.8%. Individualized risk estimation by genetic analysis may further decrease the use of chemotherapy in stage I patients. Breast cancer screening may provide an opportunity to identify cancer prone families.

Advanced rectal cancer in a young pregnant Bedouin woman.

To the Editor--Dr. Adam and Dr. Shorthouse stated that 4 of 26 patients failed with the transanal endoscopic microsurgery (TEM) method; this is not correct. Two patients with advanced tumor stage higher than T1 underwent anterior resection after TEM. This is in accordance with our oncologic protocol. It was not the TEM method that failed. We were simply proceeding with required resective surgery after TEM had provided an excision biopsy. We regard excision biopsy as being inadequate for tumor extent of T2 or greater tumor stages. Patients with abdominoperineal excision as salvage surgery with regular follow-up should not be classified as dead, even though the TEM method failed in this particular case. Adjuvant chemotherapy in a T1 carcinoma is unusual (page 973), as no positive lymph nodes were detectable in the preoperative intrarectal ultrasound scan and, of course, not in the resected specimen. The patient concerned was given adjuvant therapy at his own risk and demand, trying to reach optimum security of therapy. We were only informed about his treatment during the follow-up re-examinations. Adjuvant therapy was not part of the treatment schedule of the T1 rectal carcinomas. Accordingly, any doubts of colleagues concerning the influence of adjuvant therapy and, thus, delaying the onset of recurrence are unfounded. We assumed that only a comparison of the two different operative techniques was intended. We also appreciate and respect the doubts of colleagues concerning local surgery for cancer, as we harbored doubts ourselves before this study was done. Even now we are kept vigilant during the follow-up, until all patients have completed at least a five-year study period. We, however, hope that the TEM method makes local surgery safer than it previously was.

Ipsilateral Breast Carcinoma Following Treatment for Primary Breast Lymphoma

Background: The breast is an unusual site for primary non-Hodgkin’s lymphoma. Carcinoma in the same breast after treatment for lymphoma poses therapeutic challenges, but there is only 1 case report in Japanese, which describes this occurrence. Patient and Methods: A 59-year-old woman was diagnosed with infiltrating ductal carcinoma of the breast after receiving doxorubicinand vincristine-based chemotherapy for ipsilateral primary large cell breast lymphoma. The cancer was of high grade histology, with immunohistochemistry staining 3+ positive for HER2/neu. Results: After lumpectomy and sentinel node biopsy, adjuvant paclitaxel without anthracyclines was given but had to be stopped early because of neurotoxicity. Radiotherapy to the breast was administered, and a 1-year course of trastuzumab was planned. Conclusion: Breast cancer can occur after breast lymphoma. For primary breast lymphoma, cumulative doses of cardiotoxic and neurotoxic drugs should be limited to 3-4 cycles of chemotherapy, using treatment protocols for stage I-II large cell lymphoma. Consolidation radiotherapy should be considered at a dose curative for microscopic breast cancer.

Dedicated Screening Mammography for Diagnosis of Small Breast Cancer

Breast cancer is the most common malignancy in women, and early diagnosis is a cornerstone of successful treatment. Mammography is the sole acceptable method for breast cancer screening, but its efficacy is still disputable. The aim of this study was to determine whether the influence of dedicated mammographic team skills could improve the diagnostic accuracy of screening mammography and detection of small breast cancers. From June 1992 to September 1996 a total of 17,393 screening mammograms and 335 mammographically guided needle-localization breast biopsies were performed. From August 1994, a dedicated mammographer commenced work in our hospital. Screening mammography and biopsy results were compared for the nondedicated period (NDP) and the dedicated period (DP). The biopsy rate decreased from 2.9% to 1.3% (p < 0.0001), and the positive biopsy rate increased from 26.3% to 48.2% (p < 0.0001) during the respective periods. The cancer detection rate not changed significantly (p = 0.27) through the whole study period, but the subgroup of small carcinomas (T0, T1a, T1b) increased significantly (p < 0.04), from 25 cases in the NDP to 40 cases in the DP. We concluded that dedicated mammography team skills can significantly improve the detection of small breast cancers and permit more effective diagnosis of breast cancer by reducing the number of breast biopsies ultimately found to be benign.

Immediate reconstruction of the chest wall by latissimus dorsi and vertical rectus abdominis musculocutaneous flaps after radical mastectomy for a huge pleomorphic liposarcoma.

Abstract We describe a 53-year-old woman who had a huge pleomorphic liposarcoma of the left breast. She had a left Halstead mastectomy, which left a huge defect in the chest wall. We did an immediate reconstruction of the chest wall with combined latissimuss dorsi musculocutaneous (for the upper half of the defect) and vertical rectus abdominis musculocutaneous flaps (for the lower half of the defect). She then had radiotherapy and chemotherapy during which time the flaps remained viable and provided satisfactory coverage for the irradiated area. Unfortunately four months later she was diagnosed with spinal cord and lung metastases and died seven months after the operation.