A case of breast cancer with large cancer ulcer and multiple bone and liver metastasis responding to combination therapy of radiation and chemotherapy

We report a case of breast cancer in a 58-year-old female patient. In 2005, she was hospitalized for therapy of left breast cancer. The tumor observed was accompanied by invasion of the skin and ribs. At the same time, multiple liver and bone metastases were also observed(solid tubular adenocarcinoma, ER(+), PgR(±), HER2(3+), T4NxM1, stage IV). She was started on radiation therapy and chemotherapy(paclitaxel+trastuzumab). While the liver and bone metastases remained unchanged, the primary focus became noticeably smaller. In the course of follow-up visits, we began to administer her paclitaxel biweekly. This treatment, however, worsened her liver metastases and led us to switch to combination chemotherapy with vinorelbine and capecitabine. After 6 courses of the therapy, her liver metastases disappeared and her tumor marker levels became normal. The combination chemotherapy was continued for 1 year and then followed by 18 months of chemotherapy with capecitabine alone until recurrence of liver metastases was observed. Capecitabine along with cyclophosphamide was orally administered, bringing her tumor marker levels down to the normal range again. After approximately 6 years from the start of treatment, the patient is still alive.     

Two cases of HER2-positive advanced or metastatic breast cancer, responding to lapatinib and capecitabine

The first patient was a 59-year-old woman who was diagnosed with invasive scirrhous carcinoma. The tumor was estrogen receptor (ER)-positive, progesterone receptor (PgR)-positive, and human epidermal growth factor receptor 2 (HER2)-positive. The patient was treated with adjuvant chemotherapy and endocrine therapy after surgery. Liver metastases developed 5 years after surgery. She was treated with trastuzumab combined with vinorelbine, paclitaxel, or docetaxel. The liver metastases increased in size, 9 years after surgery, and she was treated with lapatinib and capecitabine. The efficacy of chemotherapy was judged as a partial response. The second patient was a 74-year-old woman who was diagnosed with invasive ductal carcinoma in 2005. The tumor was ER-negative, PgR-positive, and HER2-positive; she was treated with trastuzumab and paclitaxel. She developed dyspnea in January 2010. Chest radiograph showed increased lung metastases and left pleural effusion; she was treated with lapatinib and capecitabine. Lung metastases decreased and left pleural effusion disappeared after the first cycle of chemotherapy. The efficacy of chemotherapy was judged as a partial response.     

HER2-positive,trastuzumab-resistant metastatic esophageal cancer presenting with brain metastasis after durable response to dual HER2 blockade: a case report

We here report a case of a patient diagnosed with human epithelial growth factor receptor 2 (HER2)-amplified esophageal adenocarcinoma. The patient responded well to trastuzumab-based chemotherapy initially, but progressed with liver metastases. Her treatment was then switched to dual HER2 blockade with both trastuzumab and lapatinib in combination with capecitabine. She tolerated therapy and responded remarkably well with radiographic resolution of liver metastases. Unfortunately, she developed multiple brain metastases in the absence of extracranial progression. Discordant negative expression of HER2 and subclonal mutations in brain lesions were discovered, which, at least in part, explained her brain metastases in the presence of capecitabine and lapatinib, as both agents are known to be able to cross the blood brain barrier. The potential mechanism for dual HER2 blockade is discussed in the context of HER2-positive, trastuzumab-resistant, advanced esophageal cancer. The incidence of brain metastasis in advanced gastro-esophageal cancer has been reported to be extremely low, but is expected to increase with more effective systemic therapy. The intratumoral heterogeneity between the metastases, local recurrences and the primary tumor is definitely noteworthy.     

A case of HER2-positive metastatic breast cancer responding to trastuzumab plus gemcitabine combination therapy

A 60-year-old woman was admitted to the hospital with left thigh pain. She had undergone mastectomy and axillary lymph node dissection for right breast cancer (T3N2M0) five years and two months earlier. The pathological diagnosis then was invasive ductal carcinoma with axillaryly mph node metastases. Hormone receptors and HER2 status were negative and positive (3+), respectively. The patient received adjuvant chemotherapy and radiotherapy, but bone metastases appeared 18 months after surgery. Although trastuzumab-combination chemotherapy with taxane and/or capecitabine was given, bone metastases in thoracic vertebra resulted in incomplete paralysis in both legs. She underwent thoraco-lumbar vertebral fixation 10 months before admission. A PET/CT revealed multiple bone metastases in the left femur as well as vertebrae, and CEA rose markedly. She received radiotherapy and trastuzumab monotherapy in addition to bisphosphonate. Temporarily, CEA decreased, but because recurrence nests were recognized in the supraclavicle and mediastinum after the eight-month treatment, trastuzumab monotherapy was followed by trastuzumab plus vinorelbine combined therapy. This regimen markedly reduced CEA after three months, but it rose again over the following three months. As S-1-combined therapy was not effective, trastuzumab+gemcitabine (1 g/week and two weeks on/one week off) combined therapy was started. CEA decreased markedly after 4 cycles, and FDG accumulation in the recurrence region was markedly improved. The adverse event during this treatment was minor, and PS was sufficiently maintained. These results suggest that trastuzumab plus gemcitabine combination therapy is effective for HER2-positive metastatic breast cancer.     

Complete remission of recurrent breast cancer with multiple liver metastases after oral capecitabine and injected trastuzumab

A 32-year-old woman underwent modified radical mastectomy for right breast cancer (invasive ductal carcinoma, f, INF beta, v0, ly1, pT2, pN1, M0, Stage II B ER (+/-), PR (-), Her2 (3+)) in June 2003, and received postoperative systemic adjunctive chemotherapy using epirubicin combined with cyclophosphamide, followed by paclitaxel. In August 2004, after a disease-free interval of 14 months, liver metastasis appeared, and therefore from September 2004, combination chemotherapy with oral capecitabine (2,400 mg/day) and injected trastuzumab (120 mg/week) was started. After 3 cycles, all the metastases responded and this marked response has been maintained for 16 months. This therapy is currently being continued (19 cycles), and no serious side effects have been encountered. Capesitabine and trastuzumab combination therapy is effective for recurrent breast cancer showing overexpression of HER2 and resistance to taxane, and can be considered as a first-line therapy for this purpose. It is anticipated that many cases treated with this regimen will be reported and discussed in the near future.     

Two cases of radiofrequency ablation (RFA) therapy for control of liver metastases from breast cancer

We present two cases of liver metastases from breast cancer treated by radiofrequency ablation (RFA) for elongation of life. Case 1: A 50-year-old woman was treated by left mastectomy (stage IIIa) in December 2002. In April 2004, she was treated with a combination therapy of weekly paclitaxel and trastuzumab for multiple liver metastases, left supraclavicular lymph node metastases, and multiple bone metastases. After 16 courses of weekly paclitaxel and trastuzumab, liver metastases decreased significantly in size. Because liver metastases recurred during a continuation of weekly paclitaxel and trastuzumab, we performed RFA and chemotherapy using a hepatic artery infusion of docetaxel for liver metastasis. The aggravation spread to the liver lesion and she died after 20 months from liver metastases. Case 2: A 65-year-old woman was treated by left mastectomy (stage IIA) in 1984, and the distant metastasis was not found through the course after an operation. She was noted with a liver function aberration in another hospital in March 2005. We scanned it, and it was diagnosed as multiple liver and bone metastases from breast cancer. Because she did not hope for an anticancer drug treatment for multiple liver metastases, we performed RFA in May 2005. After the second RFA was performed, she does not show any new lesion to the liver for 10 months.     

A case of local advanced breast cancer with multiple lung metastases successfully treated with multimodal therapy

We report a case of local advanced breast cancer with multiple lung metastases (T4bN2M1) achieving a significant improvement of QOL by multimodal therapy with chemotherapy, antibody therapy, radiation therapy and surgery. The patient was a 47-year-old woman with mental deterioration who had an ulcerative breast cancer with multiple lung metastases. Breast biopsy led to a diagnosis of an invasive ductal carcinoma positive for erbB2 protein expression. She received 6 cycles of tri-weekly docetaxel (60 mg/m2) and weekly trastuzumab. Although metastases in the lung disappeared after chemotherapy, the response of breast ulceration was less satisfactory. Simple mastectomy followed by radiation therapy (50 Gy) to the axilla was performed as a palliative treatment. No signs of recurrence were observed for more than 14 months of treatment by trastuzumab. Multimodal therapy can improve patient QOL and the clinical outcomes in Stage IV local advanced breast cancer.     

Randomized phase II study of lapatinib plus capecitabine or lapatinib plus topotecan for patients with HER2-positive breast cancer brain metastases

Approximately one-third of patients with advanced, HER2-positive breast cancer develop brain metastases. A significant proportion of women experience central nervous system (CNS) progression after standard radiation therapy. The optimal treatment in the refractory setting is undefined. This study evaluated the toxicity and efficacy of lapatinib in combination with chemotherapy among patients with HER2-positive, progressive brain metastases. Patients with HER2-positive breast cancer with progressive brain metastases after trastuzumab and cranial radiotherapy were included. The primary endpoint was CNS objective response, defined as a ≥50% volumetric reduction of CNS lesion(s) in the absence of new or progressive CNS or non-CNS lesions, or increasing steroid requirements. The study was closed early after 22 of a planned 110 patients were enrolled due to excess toxicity and lack of efficacy in the lapatinib plus topotecan arm. The objective response rate (ORR) in the lapatinib plus capecitabine arm was 38% (exact 95% confidence interval [CI] 13.9–68.4). No responses were observed in the lapatinib plus topotecan arm. Although the study was stopped prior to full enrollment, some promising indications of CNS activity were noted for lapatinib plus capecitabine. The combination of lapatinib plus topotecan was not active and was associated with excess toxicity.     

Trastuzumab-based Retreatment after Lapatinib in Heavily Pretreated HER2 Positive Metastatic Breast Cancer: an Anatolian Society of Medical Oncology Study

Background: For HER2 positive metastatic breast cancer (MBC), continuing anti-HER2 therapy beyondprogression is associated with improved outcome. However retreatment with trastuzumab after lapatinibprogression is controversial. We retrospectively analyzed the efficacy of trastuzumab-based chemotherapy inHER2+ metastatic breast cancer patients whose disease progressed after lapatinib. Materials and Methods:Between October 2010 and May 2013, 54 patients whose disease progressed after lapatinib were retreated withtrastuzumab-based chemotherapy. Efficacy and toxicity results were evaluated retrospectively. Results: Themedian age of patients was 46 (range 27-67). Fourteen patients (26%) had metastases at the time of diagnosis.All of the patients had received trastuzumab in an adjuvant or metastatic setting, while 16 (30%) had receivedtwo lines of trastuzumab. All patients had received lapatinib plus capecitabine. The median chemotherapyline for the metastatic setting was 2 (range 1-7). Cranial metastases were identified in 27 (50%) patients. 53patients received trastuzumab-based chemotherapy following lapatinib progression while one patient receivedtrastuzumab monotherapy. Combination chemotherapy consisted of navelbin (n=33), taxane (n=10), gemcitabine(n=2), platinum (n=2) and platinum with taxane (n=6). The median treatment cycle was 5 (range 1-44). Among 49patients assessed for response 2 (4%) showed CR, 12 (25%) PR, 11 (22%) SD and 24 (49%) disease progression.Asymptomatic cardiotoxicity was reported in 2 (4%) of the patients. At a median follow-up of 9 months (1-39),median progression-free survival was 5 months (95% CI 4.1-5.9) and median overall survival was 10 months(95% CI 6.9-13.0). PFS and OS were not affected by the absence/presence of cranial metastases. Conclusions:Retreatment with trastuzumab-based therapy after lapatinib progression showed efficacy in heavily treatedMBC patients.     

Clinical recommendations for the use of lapatinib ditosylate plus capecitabine for patients with advanced or metastatic HER2-positive breast cancer

Primary and acquired resistance to trastuzumab pose a therapeutic challenge when treating patients with HER2 (erbB-2)-positive locally advanced or metastatic breast cancer (MBC). The recent introduction of lapatinib (Tykerb/Tyverb, GlaxoSmithKline, Brentford, UK) provides a new management option for such patients. A prospective, randomized phase III clinical trial has confirmed that lapatinib in combination with capecitabine extends time to progressive disease in HER2-positive MBC, compared with capecitabine alone in patients with disease progression despite prior anthracycline, taxane and trastuzumab therapy. Preliminary data also indicate that lapatinib may exert a beneficial effect on brain metastases, a common sanctuary site for HER2-positive breast cancer following trastuzumab treatment. The tolerability of lapatinib is commensurate with that of other erbB family tyrosine kinase inhibitors and no significant new adverse events have emerged following its introduction into clinical practice. In particular, no additive cardiotoxicity has been observed when lapatinib is prescribed after trastuzumab therapy. Based on the published literature and supplemented by clinical experience, this article provides practical management recommendations for the use of lapatinib plus capecitabine in patients with MBC. Issues addressed include patient selection, baseline evaluation and monitoring for clinical benefit. The minimization and management of adverse events is also discussed in detail, particularly the dermatological and gastrointestinal effects, which are the most clinically significant side-effects of lapatinib therapy. Further recommendations cover the minimization of drug interactions, anticipated dosing alterations and the optimal employment of oral anticancer regimens.     

Complete response in HER2+ leptomeningeal carcinomatosis from breast cancer with intrathecal trastuzumab

Trastuzumab, a monoclonal antibody against the HER2 receptor, is a major breakthrough in the treatment of HER2+ breast cancer. However, its high molecular weight precludes it from crossing the intact blood–brain barrier, making the central nervous system a sanctuary to HER2+ breast cancer metastases. We prospectively assessed functional outcome and toxicity of administering trastuzumab directly into the cerebrospinal fluid of a patient with leptomeningeal carcinomatosis (LC) and brain metastases from HER2+ breast cancer that had already been treated with other intrathecal chemotherapy, with no benefit. Upon signed informed consent, weekly lumbar puncture with administration of trastuzumab 25 mg was begun to a 44 year-old women with metastatic breast cancer (lymph node, bone, lung, and liver involvement) previously treated with tamoxifen, letrozole, anthracyclines, taxanes, capecitabine, intravenous trastuzumab, and lapatinib. She received 67 weekly administrations of intrathecal trastuzumab with marked clinical improvement and no adverse events. She survived 27 months after LC diagnosis. A complete leptomeningeal response, with no evidence of leptomeningeal metastasis at necropsy, was achieved. We believe that intrathecal trastuzumab administration should be prospectively evaluated to confirm clinical activity and optimize dose, schedule, and duration of treatment.     

Drug Insight: intracellular inhibitors of HER2--clinical development of lapatinib in breast cancer

Targeting the human epidermal growth factor receptor type 2 (HER2) in breast cancer patients whose tumors overexpress HER2 has been clearly demonstrated to be effective in clinical trials with the monoclonal antibody trastuzumab. Not all patients, however, respond to trastuzumab therapy. Lapatinib is an oral receptor tyrosine kinase inhibitor that targets HER2 and the EGFR. Preclinical data reveal that lapatinib has activity in trastuzumab-resistant cell lines as well as synergistic activity with trastuzumab. In a pivotal phase III trial, a combination of lapatinib and capecitabine significantly decreased the risk of disease progression relative to capecitabine alone in women with HER2-positive advanced or metastatic breast cancer previously treated with anthracyclines, taxanes, and trastuzumab. Other trials are evaluating lapatinib in inflammatory breast cancer--for which encouraging data have been reported--in combination with hormone therapy, in combination with trastuzumab, and as an adjunct to adjuvant therapy for early-stage disease. Notably, lapatinib has not been associated with serious or symptomatic cardiotoxicity in clinical trials. It can cross the blood-brain barrier and might therefore have a role in preventing central-nervous-system progression. These features make lapatinib an ideal agent to evaluate more fully in HER2-positive metastatic and early-stage breast cancer.     

Effective combination chemotherapy using weekly trastuzumab and paclitaxel in the treatment of a recurrent breast cancer patient with liver metastases

A 48-year-old woman was diagnosed with multiple locoregional recurrence five months after receiving breast conserving surgery, and she underwent mastectomy. CEF therapy was combined following surgery; however, lung metastases developed 9 months after the initial surgery. A CR has been observed after monthly use of docetaxel alone for 14 months. Since multiple liver metastases were detected 17 months later, the patient was given monthly docetaxel infusions for 2 months followed by weekly trastuzumab infusions for 8 weeks, resulting in PD. Thereafter, combination of weekly trastuzumab with paclitaxel was used and a nearly CR remained for 10 months. Although multiple brain metastases were seen 36 months later, vertigo was mostly controlled with whole brain radiotherapy. Combination of weekly trastuzumab and paclitaxel therapy is effective for liver metastases from breast cancer and useful considering the slight side effects and possibility of long-term administration.     

Ki-67 index as a prognostic factor of subsequent lapatinib-based therapy in HER2-positive metastatic breast cancer with resistance to trastuzumab

Prognostic factor analysis has been conducted to determine whether the parameters of clinical data and biomarkers would predict differential progression-free survival (PFS) or overall survival (OS) from lapatinib-based therapy in patients with primary or acquired resistance to trastuzumab. Treatment with lapatinib plus capecitabine for HER2-positive metastatic breast cancer (MBC) with primary or acquired resistance to trastuzumab was analyzed retrospectively. Tumor biomarkers, which came from the biopsies before the starting of lapatinib therapy, were evaluated by immunohistochemistry (IHC). Prognostic factors related to PFS or OS of the lapatinib therapy were assessed by univariate and multivariate analysis. Ki-67 index and liver metastases were the significant prognostic factors for predicting PFS of subsequent lapatinib therapy in the univariate analysis and the multivariate analysis. The risk for disease progression in patients who had a Ki-67 index < 40% was 59% less than that in patients had Ki-67 ≥ 40 (HR = 0.41, 95% CI, 0.23–0.74, P = 0.003). TTP of prior trastuzumab therapy, liver metastases, and the number of metastatic sites were three independent prognostic factors of subsequent lapatinib therapy. Ki-67 index was the significant prognostic factors for predicting PFS of the subsequent second line targeted therapy in patients with trastuzumab resistance.     

Lapatinib plus trastuzumab for a patient with heavily pre-treated gastric cancer that progressed after trastuzumab

A 57-year-old female with advanced gastric cancer was referred to our hospital. She underwent neoadjuvant chemotherapy with S-1 plus cisplatin followed by curative gastrectomy. Weekly paclitaxel and combination chemotherapy with irinotecan plus cisplatin were administered for lymph node recurrence, but the tumor progressed. Since the human epidermal growth factor receptor 2 status of her gastric cancer specimen was strongly positive, docetaxel plus trastuzumab was administered for three cycles. However, the lymph node metastasis appeared to enlarge and abdominal pain worsened. Therefore, combination chemotherapy with lapatinib and weekly trastuzumab was initiated. A computed tomographic scan after 3 months of treatment showed stable disease. Although dose reduction of lapatinib was necessary due to Grade 3 diarrhea, the patient has continued this treatment on an outpatient basis without signs of disease progression for 8 months after initiation. In this case, trastuzumab plus lapatinib resulted in durable stable disease, despite the appearance of progression during prior chemotherapy with trastuzumab.     

A case of liver metastases of breast cancer successfully treated by combination chemotherapy using hepatic arterial infusion of docetaxel and systemic administration of trastuzumab

A 43-year-old woman underwent breast-conserving therapy for right breast cancer with multiple liver metastases (pT3N3aM1, stage IV, ER (-), PgR (-), HER2 (3+)), in November, 2002. Following surgery, she received combination chemotherapy using hepatic arterial infusion of docetaxel and systemic administration of trastuzumab weekly. During therapy, no serious side effects and only grade 1 nausea were observed; after 3 courses, therapy was safely continued on an outpatient basis. Metastatic liver tumors responded to the treatment, and they completely disappeared on an abdominal CT 5 months later. In addition, all elevated tumor markers in serum decreased to the normal range. No new metastatic or recurrent lesions were found 14 months after surgery. We conclude that this combination chemotherapy is safe and may be very useful for the treatment of breast cancer patients with liver metastasis.     

A Successfully Resected Case of Recurrent Lung and Liver Metastases of Rectal Cancer Treated with XELIRI + Bevacizumab Therapy

It has been reported that many colorectal cancer (CRC) patients with synchronous or metachronous liver metastases underwent surgery subsequent to neoadjuvant combination chemotherapy with folinic acid, fluorouracil, and oxaliplatin (FOLFOX), folinic acid, fluorouracil, and irinotecan (FOLFIRI), or capecitabine and oxaliplatin (XELOX). However, there are very few reports of the use of capecitabine and irinotecan (XELIRI). We herein report a successfully resected case of recurrent lung and liver metastases of rectal cancer treated with combination chemotherapy with XELIRI + bevacizumab (BV) therapy. A 63-year-old male developed recurrence of a solitary nodule in the right lower lobe of the lung and multiple liver metastases after low anterior resection for rectal cancer 1 year previously. Partial resection of the right lower lobe of the lung was performed and treatment with XELIRI + BV was initiated. A computed tomography scan revealed a reduction in tumor size without any new lesions after four cycles of XELIRI + BV therapy. Partial hepatectomy of S1, S5, and S7 was safely performed. The patient is now undergoing adjuvant chemotherapy and has been free from recurrence for 18 months following surgery. There are only few studies with relatively low patient numbers reporting on the outcome after resection of both pulmonary and hepatic metastases of CRC. We therefore report a patient who underwent sequential resection of pulmonary and hepatic metastases with XELIRI + BV therapy.Key words: Colorectal cancer, Liver metastasis, XELIRI     

Markedly effective regimen using bi-weekly trastuzumab and paclitaxel in an advanced breast cancer with multiple liver metastases

A 69-year-old woman had a 7 x 6 cm tumor on her left breast with ipsilateral axillary lymph node swelling and multiple liver metastases as detected on CT scan (T 3 N 2 M 1 b, Stage IV). Core needle biopsy and immunohistochemistry of breast tumor showed invasive ductal carcinoma with negative hormone receptor and overexpression of HER 2. After a treatment failure of 3 months weekly trastuzumab monotherapy, a combination of bi-weekly trastuzumab and paclitaxel (weekly 6, bi-weekly 9 courses), was given. Tumor markers became negative 4 months later, and multiple liver nodules, breast tumor and axillary nodes completely disappeared 9 months later. Breast surgery was avoided, and CR was maintained more than 8 months only with bi-weekly trastuzumab. From the standpoint of the patient's convenience,a bi-weekly schedule of trastuzumab and paclitaxel could be a promising treatment choice for metastatic breast cancer.     

Lapatinib and breast cancer: current indications and outlook for the future

Lapatinib is an oral dual erbB 1/2 tyrosine kinase inhibitor that inhibits human EGF receptor 2 (HER2) and blocks the EGF receptor. Studies have shown that in patients with metastatic HER2-positive breast cancer that is resistant to trastuzumab, the addition of lapatinib to capecitabine improves progression-free survival and appears to lengthen overall survival. Furthermore, lapatinib has been studied in patients with involvement of the CNS and has been associated with stable disease and some responses. Its combination with letrozole provided an improvement in progression-free survival compared with single-agent letrozole in women with hormone receptor-positive, HER2-positive metastatic breast cancer. More recently, data suggested that the combination of lapatinib with trastuzumab significantly improves overall survival in women with metastatic breast cancer compared with single-agent lapatinib. Current indications in the USA for the use of lapatinib are for the treatment of metastatic HER2-positive breast cancer, both in combination with capecitabine in patients who have received taxane, anthracycline and traztuzumab, and in combination with letrozole for postmenopausal patients with hormone receptor- and HER2-overexpressing breast cancer. Common side effects of lapatinib include diarrhea and rash. Studies to date have found a less than 2% risk for cardiotoxicity, although most cardiac events that occurred during the studies were not attributed to lapatinib. It is important to consider that most of the patients in existing studies had already been treated with trastuzumab with no significant cardiotoxicity; therefore, future studies will show how trastuzumab-naive patients tolerate lapatinib. Ongoing research is evaluating the role of lapatinib in the adjuvant setting as a single agent or in combination with trastuzumab.     

Neoadjuvant Dual HER2‐Targeted Therapy With Lapatinib and Trastuzumab Improves Pathologic Complete Response in Patients With Early Stage HER2‐Positive Breast Cancer: A Meta‐Analysis of Randomized Prospective Clinical Trials

Background.

Randomized clinical trials (RCT) that evaluated the addition of lapatinib to trastuzumab plus neoadjuvant chemotherapy (NAC) in patients with HER2-positive, operable breast cancer revealed a questionable improvement in pathologic complete response (pCR) rate. We performed a meta-analysis of prospective RCTs that examined the effect of adding lapatinib to trastuzumab and NAC on pCR rate.

Methods.

PubMed databases and abstracts from the proceedings of the American Society of Clinical Oncology and the San Antonio Breast Cancer Symposium were searched for RCTs that compared lapatinib plus trastuzumab and NAC with trastuzumab in combination with NAC and that included pCR as the primary outcome. Our main objective was to estimate the effect of adding lapatinib to trastuzumab plus NAC on pCR rate, defined as no residual invasive cancer in breast and axillary lymph nodes.

Results.

In total, 1,017 patients with early stage breast cancer from 5 trials were included. Four trials examined the addition of lapatinib to trastuzumab plus NAC; this resulted in statistically significant improvement in pCR, defined as no residual carcinoma in breast and lymph nodes. The pCR rate was 55.76% and 38.36% in the lapatinib plus trastuzumab and the trastuzumab plus NAC arms, respectively (odds ratio [OR]: 1.94; 95% confidence interval [CI]: 1.44–2.60). In three trials, the rates of pCR, defined as no residual invasive carcinoma in breast only, for the lapatinib plus trastuzumab and trastuzumab-alone groups were 55.01% and 40.70%, respectively, also resulting in significant improvement (OR: 1.78; 95% CI: 1.27–2.50).

Conclusion.

The addition of lapatinib to trastuzumab in combination with neoadjuvant chemotherapy significantly improves pCR rates in patients with HER2-positive breast cancer.