Real-life clinical pattern, management, and survival in Thai patients with early-stage or metastatic triple-negative breast cancer.

OBJECTIVES: To characterize the clinical pattern and evaluate real-life practices in the management of patients with triple-negative breast cancer (TNBC) in Thailand. METHODS: In this multicenter, prospective, observational cohort, females (aged ≥18 years) with histologically and immunohistochemically confirmed TNBC were enrolled. Patient data was collected at four study visits-an inclusion visit (for enrollment), and three subsequent follow-up visits at 12±1, 24±1, and 36±1 months after completion of first day of any planned chemotherapy. RESULTS: Of the 293 enrolled patients, 262 (89.4%) had early-stage TNBC (Stage I: 46 patients, Stage II: 151 patients, and Stage III: 65 patients) and 31 (10.6%) had metastatic TNBC (mTNBC). Chemotherapy was prescribed to 95.4% of the early-stage patients and to 100.0% of the mTNBC patients; most commonly as anthracycline-based in combination with cyclophosphamide and other agents. Patients' performance status and consensus guidelines were the major factors affecting choice of treatment. In early-stage patients, median disease-free survival (DFS) and overall survival (OS) had not been reached for Stage I and II patients, and were calculated to be 37.0 months and 40.0 months, respectively, in Stage III patients. In mTNBC patients, progression-free survival (PFS) and OS were found to be 10.0 months and 14.0 months, respectively. In Stage III patients, anthracycline-based regimens were found to be associated with increase in DFS (p = 0.0181) and OS (p = 0.0027) compared to non-anthracycline-based regimens. In mTNBC patients, non-taxane-based regimens were associated with an increase in PFS (p = 0.0025). The 3-year survival rates in early-stage and mTNBC patients were 85.0% and 21.0%, respectively. CONCLUSION: Clinical management of TNBC in Thailand follows the general guidelines for treatment of TNBC. However, prognosis and survival outcomes are suboptimal, especially in progressive disease. This study is the first assessment in the existing practices in which the results could pave to way to improve the treatment outcome of TNBC in Thailand.

Nipple-Areola Complex Sensation after Nipple-sparing Mastectomy.

BACKGROUND: Nipple-sparing mastectomy (NSM) has been proven to be oncologically safe for treating breast cancer. This procedure had been developed to optimize the esthetic outcome and reduce feeling mutilation after mastectomy. Risks of necrotic complications and diminishing nipple-areola complex (NAC) sensation are common complications affecting the patient's satisfaction after the surgery. The evaluation of NAC sensation should be also investigated. METHODS: We prospectively analyzed 55 NSMs that were performed on 52 patients for both therapeutic and prophylactic indications in Ramathibodi Hospital from May 2007 to September 2015. Patients' demographics, operative details, oncologic outcome, and postoperative complications, focusing on NAC sensation and necrotic complications, were analyzed. RESULTS: Forty-seven NSMs (87%) were performed for therapeutic indications, and another 7 NSMs (13%) were risk-reducing operations. Of the 43 patients performing NSM for breast cancer treatment, 33 patients (77%) had invasive cancer and 11 patients (23%) had ductal carcinoma in situ. One subareola base tissue was found an occult cancer, and the NAC was then removed. There were 3 locoregional recurrences after a median follow-up time of 24 months (range, 2-104 months). The NAC sensation was evaluated in a total of 35 patients. Twenty-five patients (46%) underwent serial evaluation after 6 months of operation, and 10 patients were evaluated at more than 1 year after operation. In the first 6 months, 11 patients (44%) showed partial sensation recovery, and 3 more patients had partial recovery after 1-year follow-up. Only 1 patient (2%) had complete sensation recovery in all area of the NAC. In late evaluation group, 7 out of 10 patients had partial recovery. Most pain sensation remained in the lower aspect of the areola away from surgical incision. CONCLUSIONS: NSM is technically feasible in selected patients with low rates of NAC removal. Some patients can preserve the NAC sensation. Long-term outcome should receive follow-up.

Malignant transformation of phyllodes tumor: a case report and review of literature.

Malignant phyllodes may transform from benign phyllodes; low-aggressive malignant phyllodes tumor is manageable by locally wide excision.

Complications and oncologic outcomes of pedicled transverse rectus abdominis myocutaneous flap in breast cancer patients.

BACKGROUND: There are several techniques for harvesting the pedicled transverse rectus abdominis myocutaneous (TRAM) flap after mastectomy in breast cancer patients. We examined the whole muscle with partial sheath sparing technique and determined factors associated with its complications and oncological outcomes. METHODS: We retrospectively reviewed the results of 168 TRAM flaps performed between January 2003 and December 2010, focusing on complications and oncologic outcomes. RESULTS: Among the 168 pedicled TRAM flap procedures in 158 patients, flap complications occurred in 34%. Most of the flap complications included some degree of fat necrosis. There was no total flap loss. Flap complications were associated with elderly patients and the presence of major donor site complications. Abdominal bulging and hernia occurred in 12% of patients. The bi-pedicled TRAM flap and higher body mass index (BMI) were significant factors associated with increased donor site complications. Seven patients (4%) developed loco-regional recurrence. Within a median follow-up of 27 months, distant metastasis and death occurred in 6% and 4% of patients, respectively. CONCLUSIONS: The pedicled TRAM flap using the whole muscle with partial sheath sparing technique in the present study is consistent with the results from previous studies in flap complication rates and oncological outcomes.

Effect of young age, positive margins, and triple negative status on disease recurrence after breast conserving therapy.

BACKGROUND: To determine the risk factors for disease recurrence after breast conserving therapy (BCT) for breast cancer in a group of South-East Asian women. METHODS: Medical and pathological records of women who underwent BCT during the 10-year period from 2001 to 2010 were reviewed. Data collected included age ≤35 years defined as the young, type of operation, pathological data, hormonal receptor (HR) status, human epidermal growth factor receptor-2 (HER-2) expression status, and surgical margin status. Data on adjuvant therapy were also collected. Main outcomes were overall breast cancer recurrence, locoregional, and distant recurrence. Risk factors for each type of recurrence were identified using Cox proportional hazards regression models. RESULTS: There were 294 BCTs in 290 patients during the study period. The overwhelming majority (91%) had early stage (stages I-II) breast cancers. Young age patients constituted 9% of all patients, and triple negative cancers (HR negative and HER-2 negative) were seen in 19%. Involved margins on initial surgery were found in 9% of cases, and after reoperation, only 2% had involved margins. After a median follow-up of 50 months, and a maximum follow-up of 135 months, there were 30 recurrences and 6 deaths. Of the 30 recurrences, 19 included locoregional, 20 included distant, and 13 had in-breast recurrences. The disease-free survival at 10 years was 82.5% (95% CI: 74.8% to 88.1%), and the cumulative in-breast recurrence was 9.3% (95% CI: 4.9% to 17.2%) at 10 years. Multivariable Cox regression analysis revealed that young age, larger tumor size, involved margins, and no breast irradiation were associated with higher risk of locoregional recurrence. Triple negative status, larger tumor size, more positive nodes, and involved margins were associated with higher risk of distant recurrence. CONCLUSIONS: We found young age to be a significant prognosticator of locoregional recurrence, and triple negative status of distant recurrence. Involved surgical margin status was associated with both recurrences. Tumor size was associated with both recurrences, and axillary lymph node metastasis was associated with distant recurrence.

Oncoplastic techniques in breast surgery for special therapeutic problems.

Resection of large tumors can be challenging, from the view point of breast preservation. Oncoplastic techniques are a valuable component of breast surgery in patients with large breast tumors who desire breast preservation. These techniques have been shown to be oncologically safe, while maintaining acceptable breast cosmesis. For locally advanced or recurrent breast cancers, the goals of surgery include local disease control and palliation of clinical symptoms. Oncoplastic surgery is also effective and oncologically safe in these situations. The need to completely remove all foci of cancers with adequate surgical margins often requires the displacement of adjacent or distant skin and soft tissue to cover the resulting soft tissue defect. Sometimes doing so can be cosmetically pleasing as well. In this article we present three special therapeutic problems in three distinct conditions, all resolved with oncoplastic techniques: the benign breast condition, malignant breast condition, and the palliative setting.

Bilateral pseudoangiomatous stromal hyperplasia in a human immunodeficiency viral-infected patient.

Pseudoangiomatous stromal hyperplasia (PASH) is an uncommon mesenchymal neoplasm of the breast demonstrating stromal myofibroblastic proliferation and having the appearance of anastomosing slit-like pseudovascular spaces lined by spindle-shaped cells. A case of nodular PASH of the bilateral breasts in a 40-year-old woman with clinically presenting with a progressive enlarged breast lump is reported. Mammographic and ultrasonographic features of the right and left breasts showed a large solid lump with well-circumscribed border measuring 4 cm × 1.7 cm × 3.4 cm and 13.8 cm × 10.9 cm × 12.1 cm, respectively. Wide excision of the right breast and quadrantectomy of the left breast were performed. The histopathological examination of the lesion showed anastomosing slit-like pseudovascular spaces. The stromal cells were immunoreactive for muscle actin (HHF35), smooth muscle actin, and progesterone receptor. Clinical and pathological findings with briefly reviewed relevant literatures are discussed. This is the first clinicopathological and radiological report of bilateral mammary nodular PASH in a human immunodeficiency viral-infected patient.

Oncoplastic technique in breast conservative surgery for locally advanced breast cancer.

Locally advanced breast cancer (LABC) should be taken into decision making when planning breast conservative surgery, but this procedure should be done on the principle of oncologic safety in order to achieve negative surgical margin and maintain aesthetic result. This procedure should be offered as the choice of treatment in selected patients.

Androgenic pathway in triple negative invasive ductal tumors: its correlation with tumor cell proliferation.

Triple negative breast cancer (TNBC) is defined by estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 negativity. Patients with TNBC frequently undergo an aggressive clinical course due to the unavailability of specific targeted therapies. Androgen receptor (AR) was reported to be expressed in up to 60% of TNBC cases but there have been controversies as to the roles of androgen signaling through AR in TNBC. Therefore, in this study, we analyzed the status of AR in combination with androgen synthesizing enzymes (5α-reductase type 1 (5αR1) and 17ß-hydroxysteroid dehydrogenase type 5 (17ßHSD5)] in order to further understand androgenic actions in TNBC. Androgen receptor, 5αR1, and 17ßHSD5 were immunolocalized in a cohort of 203 TNBC patients from Thailand and Japan. We then correlated the findings with clinicopathological characteristics (age, stage, tumor diameter, lymph node invasion, metastatic spread, Ki-67 labeling index, disease-free survival, and overall survival) of the patients. Univariate analysis revealed that AR+/enzyme+ cases were associated with a significantly lower Ki-67 labeling index than AR-/enzyme- samples. Multivariate analysis indicated the presence of significant positive correlations between AR and enzyme status in tumor cells, and between tumor diameter, lymph node invasion, and distant metastasis. Significant negative correlations were also detected between Ki-67 labeling index and AR status (P = 0.04) or 5αR1 (P < 0.001). Cox proportional hazards analysis showed that Ki-67 labeling index and stage were the only factors predicting disease-free and overall survival of the patients, although univariate Kaplan-Meier analysis revealed AR/5αR1 negativity suggested a more adverse clinical course up to 80 months after surgery. These results suggest that the presence of androgen synthesizing pathways in addition to AR expression in tumor cells could confer a better clinical outcome through suppression of cell proliferation.

Breast cancer cells in the afferent lymphatic tracts of sentinel lymph nodes.

BACKGROUND: To identify breast cancer cells in the afferent lymphatic tracts of axillary sentinel lymph nodes (SLNs). MATERIAL AND METHOD: The authors performed a prospective study of 1 00 breast cancer patients who underwent SLN biopsy between June 2009 and January 2010. The afferent lymphatic tracts of SLNs were identified by isosulfan blue or radiocolloid or both and were examined histologically. RESULTS: One hundred three SLNs and afferent lymphatic tracts were examined. The mean age of the patients was 53.2 years (range, 24 to 78 years). The median number of SLNs was 2 (range, 1 to 7). Twenty-four (24%) patients had positive SLNs. Most patients had stage I breast cancer (67%). Three patients with positive SLNs (13%) and stages IIB-IIIC breast cancers had tumor cells in the afferent tract tissue. There were no tumor cells in the afferent tracts of negative SLNs. CONCLUSION: Only a small proportion of operable breast cancer patients have tumor cells in the afferent lymphatic tract tissue of SLNs. There was a probable trend for more advanced stage breast cancer to harbor tumor cells in the afferent lymphatic tract tissue.

The relative false negative rate of isosulfan blue in detecting sentinel lymph nodes in early breast cancer.

OBJECTIVE: To determine the false negative rate of the isosulfan blue injection method of SLN detection in early breast cancer, relative to that of the combined blue dye and radiocolloid injection method. MATERIAL AND METHOD: Seventy women with early breast cancer underwent the combined method of SLN detection during the period between September 2007 and December 2008. Standard criteria for each method were used to identify SLNs. Each SLN was labeled as identified by the blue dye, the radiocolloid and as being positive or negative for cancer cells. RESULTS: Subjects were 50 years old with tumors of size 2.3 cm on the average. The average number of SLNs harvested was 2.5 nodes per subject. The detection rate for the isosulfan blue method was 91% (64/70). The relative false negative rate of the blue dye was zero (0/64). CONCLUSION: Experienced surgeons who use the isosulfan blue method of SLN detection in early breast cancer can be reasonably confident that the false negative rate of the isosulfan blue method was similar to that of the combined method.

Predictive factors of axillary lymph node metastasis in breast cancer.

OBJECTIVE: To identify clinical, radiologic and pathologic factors significantly related to axillary lymph node (ALN) metastasis in women with operable breast cancer. MATERIAL AND METHOD: Records of women with operable invasive breast cancer treated between July 2002 and May 2006 were reviewed Data on the number of axillary nodes, number of positive nodes, preoperative clinical, mammographic, and pathologic characteristics of each breast cancer were retrieved. Multiple logistic regression analyses were used to identify significant predictors of ALN metastasis. RESULTS: Records of 590 patients were reviewed Positive ALNs were found in 302 patients (51%). Independent and significant predictors of ALN metastasis included younger age, larger tumor size, presence of lymphovascular invasion, category 5 mammograms and low mammographic breast density. The combination of age less than 60 years, low mammographic breast density, category 5 mammogram, tumor larger 1 cm., and presence of lymphovascular invasion, had a specificity for predicting ALN metastasis of over 95%. CONCLUSION: A combination of clinical, radiologic, and pathologic characteristics highly specific for predicting ALN metastasis was found This prediction rule might be useful for selecting breast cancer patients for full ALN dissection without a preliminary SLNB.

Effectiveness and reliability of sentinel lymph node biopsy under local anesthesia for breast cancer.

The objective of the present study was to determine the effectiveness and reliability of sentinel lymph node biopsy (SLNB) performed under local anesthesia (LA) for patients with breast cancer, by comparing the results with those obtained under general anesthesia (GA). Between January 2006 and February 2007, SLNB was performed under LA or GA in 37 and 94 patients with clinical Tis, T1, T2 or T3 N0 breast cancer, respectively. All underwent radiocolloid and blue dye injections to identify sentinel nodes. The sentinel node detection rate, the number of nodes harvested and the number of positive nodes were compared between the two groups. The sentinel node identification rates were similar for both groups. The number of sentinel and axillary nodes removed and number of positive nodes did not differ significantly between the two groups. SLNB performed under LA is an effective and reliable alternative to SLNB done under GA.

A laparoscopic versus open adrenalectomy in Ramathibodi Hospital.

OBJECTIVE: To compare the results of laparoscopic adrenalectomy with those of open adrenalectomy in Ramathibodi Hospital. MATERIAL AND METHOD: Medical charts of 41 laparoscopic and 39 open adrenalectomy patients were reviewed Baseline characteristics and outcomes of treatment were compared between these two patient groups, using univariable statistical tests and multivariable statistical procedures. RESULTS: There were significant baseline differences between the two groups in terms of gender, body mass index, ASA class, and preoperative diagnosis. The outcomes operative time, estimated blood loss and length of hospital stay were also significantly different. After adjusting for the effects of baseline differences, laparoscopic adrenalectomy was associated with a significant reduction of length of hospital stay by 40%. CONCLUSION: Laparoscopic adrenalectomy is a safe and effective procedure and should help hasten postoperative recovery and may save the costs of hospitalization.

Thoracic epidural anesthesia (TEA) with 0.2% ropivacaine in combination with ipsilateral brachial plexus block (BPB) for modified radical mastectomy (MRM).

BACKGROUND: Breast cancer is the 2nd most common tumors in Thai women. Until now, oncologic breast surgeries are typically performed by general anesthesia (GA). However, GA cannot provide adequate postoperative pain control and routine use of parenteral opioids aggravate postoperative sedation, nausea, emesis, impaired oxygenation and depressed ventilation. Thoracic epidural anesthesia (TEA) is one of the regional anesthetic techniques that can be done by using a low dose of local anesthetic in combination with ipsilateral brachial plexus block (BPB) for axillary node dissection. TEA can provide a better pain relief without potential paralysis of respiratory muscle and sedation. MATERIAL AND METHOD: Fifty ASA PS I-III patients undergoing MRM were randomly assigned to two study groups of 25 patients each. In the TEA group, an epidural catheter was inserted at T4 to T5, and 10-15 ml of 0.2% ropivacaine was injected, then interscalene BPB was done with 8 ml of 0.2% ropivacaine. Anesthesia was maintained with 5-10 ml of 0.2% ropivacaine per hour. GA was induced with 1 microg/kg of fentanyl followed by 1.5-2 mg/kg of propofol and was maintained with sevoflurane and 70% N2O in oxygen. The authors evaluated the adequacy of anesthesia, surgical condition, postanesthetic recovery, postanesthetic analgesia and patients' satisfaction. RESULTS: The demographic data was similar in both groups. The number of patients immediately arrived at PACU with a sedation score of 1 was significantly greater in TEA group (p = 0.003) while the number of patients with an Aldrete score of 10 was greater but not statistically significant (p = 0.25). The verbal rating scale and analgesic requirement were significantly lower in the TEA group (p < 0.001 and p = 0.002 respectively). Patients' satisfaction was greater with TEA than with GA (p = 0.014). Surgical condition was similar in both groups. CONCLUSION: The present study shows that TEA combined with BPB by using a low dose of 0.2% ropivacaine is a safe and reliable alternative technique for MRM. It can provide not only effective anesthesia but also better postoperative pain relief faster anesthetic recovery and greater patient satisfaction than those of the GA technique.

Acute effects of postmastectomy radiotherapy after immediate TRAM flap reconstruction in breast cancer patients.

OBJECTIVES: To study the acute effects of radiotherapy after mastectomy and immediate transverse rectus abdominis myocutaneous (TRAM) flap reconstruction in breast cancer patients treated at Ramathibodi Hospital. MATERIAL AND METHOD: Between January 2004 and March 2005, ten breast cancer patients (age 32-51 years) were treated with postoperative radiotherapy after mastectomy and immediate TRAM flap reconstruction. Medical records of these patients were retrospectively reviewed. Radiotherapy was delivered to the chest wall and reconstructed TRAM flap using 6-MV x-ray or Cobalt-60. The total dose was 45 to 50.4 Gy delivered in 25 to 28 fractions. Patients were evaluated weekly during the course of radiation and then at 1 and 2 months after treatment completion to determine acute effects or toxicities of radiation. RESULTS: During radiation, 3 patients developed erythema or mild hyperpigmentation of the skin, and 4 developed moderate hyperpigmentation. Three patients who were treated with Cobalt-60 and/or bolus to the chest wall developed skin desquamation (1 dry desquamation, 2 moist desquamation). No patient required a treatment break because of acute side effects. One patient who received chemotherapy after radiation developed recalled moist desquamation. CONCLUSION: Radiotherapy after mastectomy and immediate TRAM flap reconstruction is well tolerated and is not associated with increased acute complication or radiation interruption. The authors have noticed that chemotherapy given after radiation was related to severe skin reaction, so it should be used with caution.