Stage I Breast Cancer in the Modern Era: A Retrospective Cohort Study of 328 Patients Diagnosed from 2002 to 2006 with a 14- year Median Follow-Up.

INTRODUCTION: This study aimed to evaluate the long-term outcomes of stage I breast cancer (BC) patients diagnosed during the current era of screening mammography, immunohistochemistry receptor testing, and systemic adjuvant therapy. METHODS: A retrospective cohort study was conducted on 328 stage I BC patients treated consecutively in a single referral center with a follow-up period of at least 12 years. The primary endpoints were invasive disease-free survival (IDFS) and overall survival (OS). The influence of tumor size, grade, and subtype on the outcomes was analyzed. RESULTS: Most patients were treated by lumpectomy, sentinel node biopsy and adjuvant endocrine therapy and most (82%) were of subtype luminal-A. Adjuvant chemotherapy was administered to 25.6 % of our cohort. Only 24 patients underwent gene expression testing, which was introduced toward the end of the study period. Mean IDFS was 14.64 years, with a 15-year IDFS of 75.6%. Mean OS was 15.28 years with a 15-year OS of 74.9%. In a Cox multivariate analysis, no clinical or pathologic variable impacted on OS and only tumor size (< 1 centimeter (cm) vs 1-2 cm), impacted significantly on IDFS. During follow-up, 20.1% of the cohort developed second primary cancers, including BC. The median time to diagnosis of a second BC was 6.49 years. CONCLUSION: The study results emphasize the importance of long-term follow-up and screening for subsequent malignancies of patients with stage I BC and support the need for using prognostic and predictive indicators beyond the routine clinicopathological characteristics in luminal-A patients.

Neoadjuvant therapy with doxorubicin-cyclophosphamide followed by weekly paclitaxel in early breast cancer: a retrospective analysis of 200 consecutive patients treated in a single center with a median follow-up of 9.5 years.

PURPOSE: We analyzed outcomes of doxorubicin-cyclophosphamide (AC) followed by weekly paclitaxel as neoadjuvant chemotherapy (NAC) for breast cancer (BC), in an everyday practice with long-term follow-up of patients. METHODS: All patients (n = 200) who received the AC-paclitaxel combination as NAC for BC at the Soroka University Medical Center from 2003 to 2012 were included in this retrospective cohort study. AC was administered on an every 3-week schedule (standard dose) until May, 2007 (n = 99); and subsequently every 2-week dose dense (dd) (n = 101). Clinical pathologic features, treatment course, and outcome information were recorded. Complete pathologic response (pCR) was analyzed according to BC subtype, dose regimen, and stage. RESULTS: Median age was 49 years; 55.5% and 44.5% of patients were clinically stage 2 and 3, respectively. Standard dose patients had more T3 tumors. Subtypes were human epidermal growth factor receptor-2 (HER2)-positive 32.5% (of whom 82% received trastuzumab), hormone receptor-positive/HER2-negative 53%, and triple negative 14.5%. Breast-conserving surgery (BCS) was performed in 48.5% of patients; only 9.5% were deemed suitable for BCS prior to NAC. Toxicity was acceptable. The overall pCR rate was 26.0% and was significantly higher in the dd group and HER2-positive patients. With a median follow-up of 9.51 years median event-free survival (EFS) and overall survival (OS) are 10.85 years and 12.61 years, respectively. Patients achieving pCR had significantly longer EFS and OS. CONCLUSION: NAC for BC with AC-paclitaxel can be safely administered in the "real-world' setting with high efficacy. Current efforts are aimed at increasing rates of pCR and identifying patients who may benefit from additional therapy or conversely, de-escalated treatment.

Bone mineral density in women newly diagnosed with breast cancer: a prospective cohort study.

Estrogen may have opposing effects on health, namely increasing the risk of breast cancer and improving bone health by increasing bone mineral density (BMD). The objective of this study was to compare dual-energy X-ray absorptiometry (DXA) BMD between women newly diagnosed with breast cancer and matched controls without breast cancer. Women newly diagnosed with breast cancer treated between April 2012 and October 2017 were prospectively enrolled. A control group was established of women with negative mammography or breast ultrasound, matched 1:1 by age, body mass index, parity, and the use of hormone replacement therapy. All those included had DXA BMD, and lab assessments at enrollment. Of 869 women with newly diagnosed breast cancer, 464 signed informed consent. Of the 344 who completed the study protocol, 284 were matched to controls. Overall, the mean age was 58 years. Compared to the control group, for the breast cancer group, the mean vitamin D level was lower (48.9 ± 19.0 vs. 53.8 ± 28.8 nmol/L, p = 0.022); and mean values were higher of total hip BMD (0.95 ± 0.14 vs. 0.92 ± 0.12 g/cm2, p = 0.002), T score (-0.38 ± 1.17 vs. -0.68 ± 0.98, p = 0.002), and Z score (0.32 ± 1.09 vs. 0.01 ± 0.88, p < 0.001). Among the women with breast cancer, no correlations were found of baseline BMD with tumor size or grade, nodal involvement, or breast cancer stage. We concluded that women with newly diagnosed breast cancer tend to have higher BMD than women with similar characteristics but without breast cancer. This implies that BMD might be considered a biomarker for breast cancer risk.

Innovative Standards in Surgery of the Breast after Neoadjuvant Systemic Therapy.

BACKGROUND: The goal of neoadjuvant systemic therapy (NST) in breast cancer is to downstage tumors and downgrade treatment. Indications are constantly evolving. These changes raise practical questions for planning of surgery after NST. SUMMARY: In this review we discuss current evolving aspects of surgery of the breast after NST. Breast-conserving surgery (BCS) eligibility increases after NST - both neoadjuvant chemotherapy (NAC) and neoadjuvant endocrine therapy. Adequate margin width in NST and upfront surgery are similar - "no tumor on ink" for invasive cancer. Oncoplastic breast surgery after NST is feasible - both for BCS and mastectomy with reconstruction. There is increasing interest in the possibility of omitting surgery in patients with a complete response to NAC. Several trials are being conducted in aim of achieving acceptable prediction of pathological complete response, by combination of imaging and percutaneous biopsy of the tumor bed, as well as assessing the safety of such an approach. KEY MESSAGES: Surgery of the breast after NST should be determined not only according to biologic and anatomic parameters at diagnosis, but is dynamic, and must be tailored according to the response to therapy. The omission of surgery in exceptional responders after NAC is being explored.

Breast cancer survivors are at an increased risk for osteoporotic fractures not explained by lower BMD: a retrospective analysis.

BACKGROUND: An association between higher bone mineral density (BMD) and the diagnosis of breast cancer (BC) has been reported. Data on the risk of osteoporotic fractures in women with BC are conflicting. AIMS: The objective of this study was to assess fracture risk adjusted for BMD in women with and without BC, and to assess whether fracture risk in BC patients is attributed to BMD or BC characteristics. METHODS: Using electronic medical records of patients who underwent dual energy X-ray absorptiometry BMD studies at Soroka University Medical Center between February 2003 and March 2011, we identified women with subsequent diagnosis of osteoporotic fractures. BC status, demographic, health characteristics, BMD, and other laboratory findings were assessed. In BC patients data on grade, stage, and treatment were collected. Primary outcome was osteoporotic fracture, analyzed by Cox proportional hazards regression models. RESULTS: During a median follow-up of 4.9 years in 17,110 women with BMD testing (658 BC patients), 1,193 women experienced an osteoporotic fracture (62 in BC and 1,131 in no-BC groups). In multivariate analysis adjusted for age, body mass index (BMI) and BMD, hazard ratio (HR) for any osteoporotic fracture in women with BC was 1.34 (P=0.026). BMD was similar among women with and without BC who fractured. BC patients who experienced an osteoporotic fracture had a trend for less-advanced BC, lower rates of chemotherapy treatment, and higher rates of tamoxifen treatment. CONCLUSIONS: BC survivors are at increased risk of an osteoporotic fracture, which is not explained by worse BMD. Chemotherapy or aromatase inhibitors did not contribute substantially to fracture risk among our BC survivors.

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.

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

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.

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.

Accuracy of sonographically guided 14-gauge core-needle biopsy: results of 715 consecutive breast biopsies with at least two-year follow-up of benign lesions.

PURPOSE: The objective of this study was to examine the diagnostic accuracy of sonographically guided 14-gauge core-needle biopsy (CNB). METHODS: Sonographically guided 14-gauge CNBs of 715 breast lesions were performed in 652 patients. Histopathologic results were correlated with imaging findings, and repeat biopsy was recommended in the cases of discordance between the radiologic and pathologic results. Long-term follow-up was used for patients with CNB findings of a benign lesion. RESULTS: Sonographically guided CNB revealed malignancy in 311 lesions (43%). Thirty-one lesions with CNB findings indicating benign conditions underwent additional image-guided or excisional biopsy because of indeterminate pathologic features, disagreement between radiologic and pathologic results, surgeon preference, or patient request. Within these 31 cases, 9 malignancies were diagnosed. The duration of follow-up for the remaining 373 benign lesions varied from 27 to 60 months. In 3 of these 373 cases, carcinoma was diagnosed at the site of CNB. The false-negative rate of 14-gauge sonographically guided CNB was 3.7%, and the sensitivity of sonographically guided CNB for the diagnosis of breast cancer was 96.3%. CONCLUSIONS: Sonographically guided 14-gauge CNB is a safe and accurate method for evaluating breast lesions that require tissue sampling. Radiologic-pathologic correlation and follow-up of benign lesions are essential for a successful breast biopsy program.

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.

Using sonography to screen women with mammographically dense breasts.

OBJECTIVE: Mammographically dense breast tissue has been reported both as a cause of false-negative findings on mammography and as an indicator of increased breast cancer risk. We conducted this study to evaluate the role of breast sonography as a second-line screening test in women with mammographically dense breast tissue. MATERIALS AND METHODS: Between January 2000 and January 2002, 1517 asymptomatic women with dense breasts and normal mammography and physical examination findings underwent physician-performed breast sonography as an adjunct screening test. Within the study group, 318 women had a first-degree family history or personal history of breast cancer. The high-risk subgroup comprised these women. The detection rate of breast cancer in this subgroup was compared with the detection rate in the remaining study population with baseline risk. RESULTS: Of 1517 women examined, seven breast cancers were diagnosed (cancer-detection rate, 0.46%). Four carcinomas were detected in high-risk women and three in women with baseline risk. The cancer-detection rate in the subgroup of high-risk women was 1.3%, significantly higher (p < 0.04) than the cancer-detection rate of 0.25% in the baseline risk subgroup. All cancers were T1 (range, 4-12 mm; mean, 9.6 mm). Sentinel lymph nodes were negative for cancer in six of seven carcinomas. CONCLUSION: Screening breast sonography in the population of women with dense breast tissue is useful in detecting small breast cancers that are not detected on mammography or clinical breast examination. The use of sonography as an adjunct to screening mammography in women with increased risk of breast cancer and dense breasts may be especially beneficial.

Cutaneous angiosarcoma of breast after lumpectomy, axillary lymph node dissection, and radiotherapy for primary breast carcinoma: case report and review of the literature.

Malignant neoplasms known to develop after external beam radiation include angiosarcoma. Although angiosarcoma developing in a lymphedematous arm after radical mastectomy is a well-known phenomenon, cutaneous angiosarcoma after radiotherapy for breast carcinoma has been rarely documented. Herein we present a case with cutaneous angiosarcoma that developed in a 69-year-old woman's breast 5 years after she underwent conservative treatment to the breast: lumpectomy, axillary lymph node dissection, and radiation therapy to the breast. The possible relation of the angiosarcoma to the initial radiotherapy, early diagnosis, and treatment is discussed.