SUMMARY: Circulating tumor cells (CTCs) are epithelial cells that are shed into the circulation from a primary or metastatic tumor. After being shed, CTCs can remain in the circulation or undergo apoptosis. Evaluation of CTCs during the course of disease and treatment has prognostic value. Because of the very low concentrations of CTCs (1 CTC in the background of millions of normal hematopoietic cells) in the peripheral blood, different technologies have been developed that will allow enrichment and detection of these CTCs.
One such technology is the CellSearch® system which is the first FDA-approved test for CTC assessment, in the peripheral blood of Metastatic Breast Cancer (MBC) patients. This automated system is able to enrich the peripheral blood sample with CTCs and the cells then are fluorescently stained for CytoKeratins (CK8,18 and 19), Common Leukocyte Antigen (CD45) and a nuclear dye (DAPI). CTCs are identified when they are CK and DAPI positive and CD45 negative. In essence, CTC assessment, is a real time, peripheral blood evaluation (“Liquid Biopsy”) in MBC patients. Previously published studies have concluded that in patients with MBC, increased levels of CTCs prior to administration of a new therapy was associated with poor outcomes and failure of CTCs to drop to below 5 CTCs per 7.5 mL of peripheral blood at 3- 5 weeks after systemic therapy initiation, predicted worse Progression Free Survival (PFS) and Overall Survival (OS), compared to those who did not have increased CTCs at baseline or had increased CTCs at baseline and but not at 3-5 weeks after therapy. With this background, a randomized study was conducted to assess whether changing treatment after one cycle of first line chemotherapy, in those with a persistent increase in CTCs, improved OS. Evaluable patients were initially divided into two groups – Group A (N=276) included patients who did not have increased CTCs at baseline and Group B (N=288) included patients who had 5 or more CTCs per 7.5 mL of peripheral blood. Eligible patients were chemotherapy naïve for MBC and were treated with single agent chemotherapy. The choice of chemotherapy was at the discretion of the attending physician. Patients in Group A remained on initial therapy until disease progression whereas patients in Group B had CTC evaluation at Day 22 and those with decreased CTCs remained on the initial therapy (N=165). Patients who had persistently increased CTCs at Day 22 (N=123), were then randomly assigned to either continue the initial therapy (Group C1) or switch to a different chemotherapy regimen (Group C2). The median Overall Survival for Groups A, B, and C (C1 and C2 combined) were 35 months, 23 months, and 13 months, respectively (P <0.001). There was no difference in median Overall Survival between Groups C1 and C2 (10.7 and 12.5 months, respectively (P = 0.98). The authors concluded that CTCs in patients with Metastatic Breast Cancer receiving first line chemotherapy has significant prognostic value and changing to a different chemotherapy regimen based on persistently increased CTCs after 3 weeks of first line chemotherapy, had no impact in prolonging Overall Survival. This group of patients (C1 and C2) should be encouraged to enroll in clinical trials as standard chemotherapy may not be as effective. CTC count can prognosticate Progression Free Survival and Overall Survival early in the treatment course thereby allowing customized care. Further, CTC enumeration, unlike mucin based serum biomarkers such as CEA and CA15-3, better correlates with clinical and pathological characteristics of the disease. Smerage JB, Barlow WE, Hortobagyi GN, et al. DOI: 10.1200/JCO.2014.56.2561
Tag: Breast Cancer
Clinical Impact of Delaying Initiation of Adjuvant Chemotherapy in Patients with Breast Cancer
SUMMARY: Breast cancer is the most common cancer among women in the US and about 1 in 8 women (12%) will develop invasive breast cancer during their lifetime. Approximately, 233,000 new cases of invasive breast cancer will be diagnosed in 2014 and 40,000 women will die of the disease. The HER or erbB family of receptors consist of HER1, HER2, HER3 and HER4. Approximately 15%-20% of invasive breast cancers overexpress HER2/neu oncogene, which is a negative predictor of outcomes, without systemic therapy. Patients with early stage breast cancer often receive adjuvant chemotherapy and this is even more so true for HER positive and triple negative (ER, PR and HER negative) breast cancer patients, who are at an increased risk to develop recurrent disease. Even though majority of the patients start their adjuvant chemotherapy within 4-6 weeks following surgery, the impact of delay in the initiation of adjuvant therapy, on outcomes, has remained unclear. Preclinical models have suggested that there is phase of increased angiogenesis and accelerated growth of micrometastases, as well as development of drug resistant clones, following removal of the primary tumor. Previously published data from a large meta-analysis had suggested that a four week delay in the initiation of adjuvant chemotherapy resulted in a 6% increase in the risk of death and an 8% increase in the risk of relapse. Based on this background information, the authors in this study evaluated the impact of time to initiation of adjuvant chemotherapy, on survival, in patients with various stages and subtypes of early stage breast cancer. In this single institution study, 6,827 women diagnosed with stages I to III breast cancer between 1997 and 2011, were categorized into one of three groups – 30 days or less, 31 to 60 days and 61 days or more, according to the time from definitive surgery to adjuvant chemotherapy. Survival outcomes were then estimated in these three groups. The median follow up was 59.3 months and majority of the patients (84.5%) had stage I or II breast cancer and 15.5% of the patients had stage III disease. The authors noted that outcomes were inferior among patients with stage II and stage III disease when chemotherapy was initiated 61 days or more after surgery, with a 76% increase in the risk of death among patients with stage III disease. This disadvantage was however not noted in patients with stage I disease. Survival estimates based on the tumor sub types revealed that patients with triple negative breast cancer tumors and those with HER-2 positive (Human Epidermal growth factor Receptor- 2) tumors, treated 61 days or more after surgery with HERCEPTIN® (Trastuzumab) based chemotherapy, had the worse survival, compared with those who initiated adjuvant treatment within the first 30 days after surgery. Patients with hormone receptor positive tumors were however not impacted. The authors concluded that delaying the initiation of adjuvant chemotherapy in patients with high risk disease such as those with Stages II and III breast cancer and those with triple negative breast cancer and HER-2 positive tumors, can negatively impact survival outcomes. de Melo Gagliato D, Gonzalez-Angulo AM, Lei X, et al. J Clin Oncol 2014;32:735-744
Phase III trial (Prevention of Early Menopause Study [POEMS]-SWOG S0230) of LHRH analog during chemotherapy (CT) to reduce ovarian failure in early-stage, hormone receptor-negative breast cancer An international Intergroup trial of SWOG, IBCSG, ECOG, and CALGB (Alliance)
SUMMARY:Breast cancer is the most common cancer among women in the US and about 1 in 8 women (12%) will develop invasive breast cancer during their lifetime. Approximately, 233,000 new cases of invasive breast cancer will be diagnosed in 2014 and 40,000 women will die of the disease. Approximately 75% of patients with breast cancer are hormone receptor positive (Estrogen Receptor/Progesterone Receptor positive) and this is a predictor of response to endocrine therapy. In premenopausal woman, the ovary is the main source of estrogen production, whereas in postmenopausal women, the primary source of estrogen is the Aromatase enzyme mediated conversion of androstenedione and testosterone to estrone and estradiol in extragonadal/peripheral tissues. Premature Ovarian Failure (POF) is a common unintended consequence of chemotherapy in premenopausal women. Besides of loss of fertility, which can influence treatment decisions in young women, ovarian failure can lead to menopausal symptoms, sexual dysfunction and loss of bone density. 
POEMS (Prevention of Early Menopause Study) is a randomized phase III trial designed to evaluate whether the addition of LHRH (Luteinizing Hormone-Releasing Hormone) analog Goserelin (ZOLADEX®), which suppresses the production of estrogens, to Cyclophosphamide based chemotherapy, would reduce POF in breast cancer patients, when compared to chemotherapy alone. Premenopausal patients less than 50 years of age, with hormone negative (ER/PR negative ), Stage I-IIIA breast cancer, scheduled to receive chemotherapy, were randomly assigned to receive standard Cyclophosphamide based chemotherapy with or without monthly ZOLADEX® . Patients in the ZOLADEX® group received 3.6 mg SQ starting 1 week prior to the first dose of chemotherapy. The primary endpoint was ovarian failure at two years (defined as amenorrhea for the prior 6 months AND post-menopausal FSH level). Other endpoints included pregnancy and survival rates. Of the 218 evaluable patients, 135 premenopausal women were evaluable for the primary end point. POF rates were 22% in the chemotherapy alone group and 8% in the ZOLADEX® group (P=0.03). When the definition of POF was more liberal to include EITHER amenorrhea or elevated FSH but not both, POF rates were 45% in the chemotherapy alone group and 20% in the ZOLADEX® group (P=0.006). Among the 218 evaluable patients, more women in the ZOLADEX® group achieved at least one pregnancy (21%) compared to 11% in the chemotherapy alone group (P=0.03). Secondary outcomes also favored the ZOLADEX® group with a Disease free Survival (DFS) rate of 78% in the chemotherapy alone group compared with 89% in the ZOLADEX® group (P=0.04) and Overall Survival (OS) rate of 82% in the chemotherapy alone group compared with 92% in the ZOLADEX® group (P=0.05). The authors concluded that the addition of ZOLADEX® to chemotherapy improved fertility prospects with a lower incidence of Premature Ovarian Failure and more pregnancies. Further, the improved Disease Free Survival and Overall Survival is an important additional perk and prevention of POF with ZOLADEX® may be a consideration not only in premenopausal patients with hormone receptor positive breast cancer but also in other malignancies such as lymphomas, when treated with similar chemotherapeutic agents. Moore HC, Unger JM, Phillips K, et al. J Clin Oncol 32:5s, 2014 (suppl; abstr LBA505)</s
KADCYLA® beneficial for patients with HER2-positive Advanced Breast Cancer who had previously received HERCEPTIN® and TYKERB®.
KADCYLA® (Ado-Trastuzumab Emtansine, T-DM1) is an antibody-drug conjugate (ADC) comprised of the antibody HERCEPTIN® (Trastuzumab) and a chemotherapy agent Emtansine, linked together. Upon binding to the HER2 receptor, KADCYLA® not only inhibits the HER2 signaling pathways but also delivers Emtansine, a microtubule inhibitor, directly inside the tumor cells and destroys them. In the TH3RESA trial, treatment with KADCYLA® significantly improved Progression Free Survival compared to physicians choice, for those patients who had previously received HERCEPTIN® and TYKERB® (Lapatinib) and this therefore makes KADCYLA® the treatment of choice, for this patient population.
A Less Intense Schedule of ZOMETA® for Patients with Metastatic Breast Cancer
Bisphosphonates inhibit osteoclast-mediated bone resorption and both oral and IV bisphosphonates reduce the risk of developing Skeletal Related Events (SRE’s) and delay the time to SRE’s in patients with Breast Cancer with bone metastases. In a study presented at ASCO 2014 meeting, continuing ZOMETA® (Zoledronic acid) for an additional year at the every 12 week schedule was non-inferior to ZOMETA® given every 4 weeks, among patients who had initially received IV bisphosphonates monthly, for one year or longer. This less frequent dosing of ZOMETA® compared with the standard monthly dosing, may be more convenient for the patients and result in less toxicities without compromising efficacy. More information at www.oncoprescribe.com
Efficacy and safety of continued zoledronic acid every 4 weeks versus every 12 weeks in women with bone metastases from breast cancer Results of the OPTIMIZE-2 trial
SUMMARY: Bone is the most common site of metastatic disease, in patients with Breast Cancer. Bisphosphonates inhibit osteoclast-mediated bone resorption and both oral and IV bisphosphonates reduce the risk of developing Skeletal Related Events (SRE’s) and delay the time to SRE’s in patients with Breast Cancer with bone metastases. Bisphosphonates can also reduce bone pain and may improve Quality of life. Of the four bisphosphonates proven to be effective in patients with Breast Cancer with bone metastases, only intravenous Pamidronate (AREDIA®) and Zoledronic acid (ZOMETA®) have been approved in the USA, whereas intravenous and oral Ibandronate and oral Clodronate have been approved in Europe. Both AREDIA® and ZOMETA® are administered every 3 to 4 weeks during the first year, following diagnoses of bone metastases. However, the optimal treatment schedule following this initial phase of treatment has remained unclear. Further, renal toxicity, long bone fractures and OsteoNecrosis of the Jaw (ONJ) have been identified as potential problems with bisphosphonate use.
OPTIMIZE-2 is a prospective, randomized, double-blind, multicenter trial, in which the authors evaluated the outcomes of a less intense schedule of ZOMETA® administered every 12 weeks, following one year of the standard initial phase of treatment with bisphosphonates. This study included 403 women with bone metastases from Breast Cancer, who had received 9 or more doses of either intravenous ZOMETA® or AREDIA®, during the first 10-15 months of therapy. The median age was 59 years and patients were randomized (1:1) to receive either ZOMETA® 4 mg IV every 4 weeks (N=200) or every 12 weeks (N=203), for one year. The primary endpoint was Skeletal Related Event (SRE) rate, defined as the proportion of patients with one or more SRE’s (pathologic fractures, spinal cord compression, need for radiotherapy or surgical stabilization of the bone). The primary analysis was non-inferiority, for the difference in SRE rates between the treatment groups. Secondary endpoints included time to first SRE, Skeletal Morbidity Rate (SMR), bone pain score, change in bone turnover markers, and safety. After a median follow up of 11.9 months, the SRE rate was 22% and 23.2% in the ZOMETA® every 4 weeks group and ZOMETA® every 12 weeks group respectively (P=0.724), suggesting that ZOMETA® given every 12 weeks was non-inferior to the q 4 week regimen. The secondary endpoints were comparable as well. More patients had renal toxicities in the ZOMETA® q 4 week group vs q 12 week group (9.6% vs 7.9%, respectively) and two cases (1.0%) of OsteoNecrosis of the Jaw (ONJ) were reported in the ZOMETA® q 4 week group. The authors concluded that the efficacy of continuing ZOMETA® for an additional year at the q 12 week schedule was non-inferior to ZOMETA® given q 4 weeks, among patients who had initially received IV bisphosphonates monthly, for one year or longer. Further the less frequent dosing of ZOMETA® compared with the standard monthly dosing, may be more convenient for the patients and result in less toxicities. Hortobagyi GN, Lipton A, Chew HK, et al. J Clin Oncol 32:5s, 2014 (suppl; abstr LBA9500)
Trastuzumab emtansine versus treatment of physician's choice for pretreated HER2-positive advanced breast cancer (TH3RESA) a randomised, open-label, phase 3 trial
SUMMARY: Breast cancer is the most common cancer among women in the US and about 1 in 8 women (12%) will develop invasive breast cancer during their lifetime. Approximately, 233,000 new cases of invasive breast cancer will be diagnosed in 2014 and 40,000 women will die of the disease. The HER or erbB family of receptors consist of HER1, HER2, HER3 and HER4. Approximately 15%-20% of invasive breast cancers overexpress HER2/neu oncogene, which is a negative predictor of outcomes without systemic therapy. HERCEPTIN® (Trastuzumab) is a humanized monoclonal antibody targeting HER2. It binds to the extracellular domain of the receptor and blocks the downstream cell signaling pathways (PI3K-AKT pathway) and induces Antibody Dependent Cellular Cytotoxicity (ADCC). HERCEPTIN® in combination with chemotherapy has been proven to significantly improve Progression Free Survival and Overall Survival in patients with advanced breast cancer. Despite this benefit, majority of these patients develop progressive disease within 18 months. The tumors in these patients continue to express HER2 although the lower sensitivity to HER2 targeted agents has been attributed to HER2 independent escape mechanisms. Treatment strategies for this patient population have included switching chemotherapy in subsequent lines of treatment and continuing HERCEPTIN®, combining another HER2 targeted agent, Lapatinib (TYKERB®) with Capecitabine (XELODA®) and dual HER2 inhibition with a combination of HERCEPTIN® and TYKERB®. KADCYLA® (Ado-Trastuzumab Emtansine, T-DM1) is an antibody-drug conjugate (ADC) comprised of the antibody HERCEPTIN® and the chemotherapy agent Emtansine, linked together. Upon binding to the HER2 receptor, it not only inhibits the HER2 signaling pathways but also delivers a chemotherapy agent Emtansine, a microtubule inhibitor, directly inside the tumor cells. This agent is internalized by lysosomes and destroys the HER2-positive tumor cells upon intracellular release.
In the EMILIA trial, KADCYLA® was associated with significant increase in Overall Survival when compared with TYKERB® and XELODA® in HER2-positive metastatic breast cancer patients, who had previously received HERCEPTIN® and a taxane. This study however excluded patients who had previously received TYKERB®. TH3RESA is an open label randomized phase III trial in which KADCYLA® was compared with treatment of physician’s choice, in patients with unresectable locally advanced, recurrent or metastatic breast cancer. Eligible patients had a left ventricular ejection fraction of 50% or more, ECOG performance status of 0-2 and had HER2-positive advanced breast cancer who had received two or more HER2-directed regimens in the advanced setting and had progressed on both HERCEPTIN® and TYKERB® containing regimens in metastatic setting and also had disease progression on a taxane, in any setting. Patients were randomized in a 2:1 ratio to receive either KADCYLA® 3•6 mg/kg intravenously every 21 days (N=404) or treatment of physician’s choice (N=198). Treatment was continued until disease progression or unmanageable toxicity. The Co-primary endpoints were Progression Free Survival (PFS) and Overall Survival. Secondary endpoints included Response Rates, duration of response, safety and quality of life. After a median follow up of 7•2 months in the KADCYLA® group and 6•5 months in the physician's treatment choice group, there was a significant improvement in Progression Free Survival with KADCYLA® compared with physician's treatment choice (6•2 months vs 3•3 months, HR= 0•528, P<0•0001). The interim Overall Survival analysis showed a trend favoring KADCYLA® (HR=0•552, P=0•0034). Patients in the KADCYLA® group had a lower incidence of grade 3 toxicities compared to the patients in the physician’s treatment choice group (32% vs 43%). Grade 3 thrombocytopenia however was more common in the KADCYLA® group compared to the physician’s choice group (5% vs 2%) and this has been attributed to the inhibition of megakaryocyte differentiation by KADCYLA®. The authors concluded that KADCYLA® should be considered the treatment of choice, for patients with HER2-positive advanced breast cancer, who have previously received HERCEPTIN® and TYKERB®. It remains to be seen however, if KADCYLA® is effective in patients who had progressed on Pertuzumab (PERJETA®) based therapies. Krop IE, Kim SB, González-Martín A, et al. Lancet Oncol. 2014;15:689-699
Randomized comparison of adjuvant aromatase inhibitor (AI) exemestane (E) plus ovarian function suppression (OFS) vs tamoxifen (T) plus OFS in premenopausal women with hormone receptor-positive (HR+) early breast cancer (BC) Joint analysis of IBCSG TEXT and SOFT trials
SUMMARY: Breast cancer is the most common cancer among women in the US and about 1 in 8 women (12%) will develop invasive breast cancer during their lifetime. Approximately, 233,000 new cases of invasive breast cancer will be diagnosed in 2014 and 40,000 women will die of the disease. Approximately 75% of patients with breast cancer are hormone receptor positive (Estrogen Receptor/Progesterone Receptor positive) and this is a predictor of response to endocrine therapy. In premenopausal woman, the ovary is the main source of estrogen production, whereas in postmenopausal women, the primary source of estrogen is the Aromatase enzyme mediated conversion of androstenedione and testosterone to estrone and estradiol in extragonadal/peripheral tissues.
Presently available therapies include Tamoxifen and other Selective ER Modulators, which modulate ER alpha activity, Aromatase Inhibitors and Ovarian ablation that decrease estrogen production and FASLODEX® (Fulvestrant) that down regulates Estrogen Receptor. Aromatase Inhibitors (AI’s) are often prescribed, due to their superiority over Tamoxifen, for postmenopausal women with Hormone Receptor positive breast tumors, in adjuvant as well as metastatic settings. AI’s however, are not effective in premenopausal women, as these individuals derive their estrogen mainly from ovaries and not extragonadal tissues. The 2000 Early Breast Cancer Trialists’ Collaborative Group (EBCTCG) overview, as well as subsequent studies comparing adjuvant ovarian ablation/suppression with adjuvant chemotherapy in premenopausal women with hormone positive breast tumors, have demonstrated similar magnitude of benefit. The TEXT (Tamoxifen and Exemestane Trial) and SOFT (Suppression of Ovarian Function Trial) are two phase III randomized trials, conducted at the same time and included premenopausal women (average age was 43 years) with hormone receptor positive early breast cancer. In the joint analysis of these two trials in which 5738 women were enrolled, the authors set out to answer 2 important questions – whether adjuvant AI improves outcomes in this patient group when their Ovarian Function is suppressed and whether there is any benefit with Ovarian Function suppression in premenopausal women suitable for adjuvant Tamoxifen. TEXT randomized patients (N=2672) within 3 months of surgery to 5 years of AROMASIN® (Exemestane) plus Ovarian Function Suppression (OFS) or 5 years of Tamoxifen plus OFS. The SOFT study randomized patients (N=3066) to 5 years of AROMASIN® plus OFS or 5 years of Tamoxifen plus OFS or 5 years of Tamoxifen alone. OFS choices included oophorectomy, ovarian irradiation or 5 years of TRELSTAR® (Triptorelin), a GnRH (Gonadotropin Releasing Hormone) agonist. The primary endpoint of these two studies was Disease Free Survival (DFS). In this joint analysis the outcomes for 4690 women randomized to receive AROMASIN® plus OFS or Tamoxifen plus OFS for 5 years, were analyzed. The 5 year Disease Free Survival was 91.1% in the AROMASIN® plus OFS group and 87.3% in the Tamoxifen plus OFS group (HR=0.72, P<0.0002). Compared to patients receiving Tamoxifen plus OFS, AROMASIN® plus OFS reduced the relative risk of premenopausal women developing a subsequent invasive breast cancer by 28% and the relative risk of breast cancer recurrence by 34%. The authors concluded that this largest joint analysis, evaluating adjuvant AI therapy with OFS in premenopausal women with Hormone receptor positive breast cancer, has demonstrated that 5 years of highly effective adjuvant endocrine therapy without chemotherapy can result in excellent outcomes. Further, AROMASIN® may be better than tamoxifen, when given with Ovarian Function Suppression. Pagani O, Regan MM, Walley B, et al. J Clin Oncol 32:5s, 2014 (suppl; abstr LBA1)
Clinical validity of circulating tumour cells in patients with metastatic breast cancer a pooled analysis of individual patient data
SUMMARY: Circulating tumor cells (CTCs) are epithelial cells that are shed into the circulation from a primary or metastatic tumor. After being shed, CTCs can remain in the circulation or undergo apoptosis. 
Evaluation of CTCs during the course of disease has prognostic value. Because of the very low concentrations of CTCs (1 CTC in the background of millions of normal hematopoietic cells) in the peripheral blood, different technologies have been developed that will allow enrichment and detection of these CTCs. One such technology is the CellSearch® system which is the first FDA-approved test for CTC assessment, in the peripheral blood of Metastatic Breast Cancer (MBC) patients. This automated system is able to enrich the peripheral blood sample with CTCs and the cells then are fluorescently stained for CytoKeratins (CK8,18 and 19), Common Leukocyte Antigen (CD45) and a nuclear dye (DAPI). CTCs are identified when they are CK positive, CD45 negative and DAPI positive. In essence, CTC assessment is a real time, peripheral blood evaluation (“Liquid Biopsy”) in MBC patients. The authors in this study conducted a pooled analysis to assess the clinical validity of CTCs in patients with MBC, as previously published studies reported contradictory results and were unable to ascertain whether enumeration of CTCs had better prognostic value than the traditional clinical and pathological features of the tumor and serum tumor markers. Data was gathered on 1944 patients with MBC, who had participated in clinical trials at 17 centers between 2003 and 2012. Participants in these studies were starting a new line of therapy (predominantly chemotherapy), and these studies had CTC quantification using CellSearch® platform, before start of new treatment (baseline), data for Progression Free Survival, Overall Survival or both. Using accepted statistical methodologies, the authors noted the following findings-
1) At baseline prior to starting treatment, 47% (N=911) patients had 5 or more CTCs per 7•5 mL of peripheral blood, suggesting more aggressive disease and this was associated with decreased Progression Free Survival (P<0•0001) and Overall Survival (P<0•0001), compared with patients with less than 5 CTCs per 7•5 mL at baseline.
2) At 3-5 weeks after start of treatment (1-2 cycles of treatment), when adjusted for baseline CTC count, 5 or more CTCs per 7•5 mL of peripheral blood was associated with shortened Progression Free Survival (P<0•0001) and Overall Survival (P<0•0001), suggesting that these patients were treatment resistant.
3) An early decrease in the CTC at week 3-5, from a high baseline of 5 or more CTCs per 7•5 mL to less than 5 CTCs per 7.5 ml was associated with significantly longer Progression Free Survival and Overall Survival.
4) Enumeration of CTCs was a better predictor of prognosis than mucin based serum biomarkers such as CEA and CA15-3.
The prognostic value of high CTC count at baseline and at 3-5 weeks of treatment, on Progression Free Survival and Overall Survival was maintained in all subgroups tested, regardless of breast cancer subtypes and type of therapy patients received. Based on this pooled analysis, with the largest assessment of CTC enumeration in MBC patients, the authors concluded that CTC count can prognosticate Progression Free Survival and Overall Survival early in the treatment course, allowing customized care. Further, CTC enumeration, unlike serum tumor markers, correlates with clinical and pathological characteristics. Bidard F, Peeters DJ, Fehm T, et al. The Lancet Oncology 2014;15:406-414
AFINITOR® overcomes Endocrine Resistance in Breast Cancer
AFINITOR® can overcome endocrine resistance in patients with Metastatic Breast Cancer. This was demonstrated in the BOLERO-2 trial in which patients who had progressed on non-steroidal Aromatase Inhibitors, when treated with a combination of steroidal Aromatase Inhibitor AROMASIN® (Exemestane) and AFINITOR® (Everolimus), had significantly improved Progression Free Survival and Clinical Benefit. AFINITOR® is a mTOR inhibitor and mTOR pathway has been implicated as one of the mechanisms for endocrine resistance in Breast cancer. A recent BOLERO-2 trial update, was published in the Breast Cancer Research and Treatment 2013.