PURPOSEWe questioned the impact of pregnancy on disease-free survival (DFS) in women with history of breast cancer (BC) according to estrogen receptor (ER) status. PATIENTS AND METHODSA multicenter, retrospective cohort study in which patients who became pregnant any time after BC were matched (1:3) to patients with BC with similar ER, nodal status, adjuvant therapy, age, and year of diagnosis. To adjust for guaranteed time bias, each nonpregnant patient had to have a disease-free interval at least equal to the time elapsing between BC diagnosis and date of conception of the matched pregnant one. The primary objective was DFS in patients with ER-positive BC. DFS in the ER-negative cohort, whole population, and overall survival (OS) were secondary objectives. Subgroup analyses included DFS according to pregnancy outcome and BC-pregnancy interval. With a two-sided α = 5% and β = 20%, 645 ER-positive patients were required to detect a hazard ratio (HR)= 0.65.ResultsA total of 333 pregnant patients and 874 matched nonpregnant patients were analyzed, of whom 686 patients had an ER-positive disease. No difference in DFS was observed between pregnant and nonpregnant patients in the ER-positive (HR = 0.91; 95% CI, 0.67 to 1.24, P =.55) or the ER-negative (HR = 0.75; 95% CI, 0.51 to 1.08, P =.12) cohorts. However, the pregnant group had better OS (HR = 0.72; 95% CI, 0.54 to 0.97, P =.03), with no interaction according to ER status (P =.11). Pregnancy outcome and BC-pregnancy interval did not seem to impact the risk of relapse. CONCLUSIONPregnancy after ER-positive BC does not seem to reduce the risk of BC recurrence.

BACKGROUND: Pregnancy-associated breast cancer (PABC) is relatively rare with considerable controversy regarding its prognosis. PATIENTS & METHODS: Two of the authors independently performed a literature search with no date or language restrictions. Eligible studies were control-matched, population-based and hospital-based studies that addressed the outcome of patients diagnosed during pregnancy or 1-year afterwards. The primary and secondary end-points were overall and disease-free survival respectively. Pooling of data was done using the random effect model. RESULTS: 30 studies were included in this meta-analysis (3,628 cases and 37,100 controls). PABC patients had a significantly higher risk of death compared to those with non-pregnancy-related breast cancer (pooled hazard ratio (pHR): 1.44; 95% CI [1.27-1.63]). The same results were encountered on restricting the analysis to HRs of multivariate analyses (pHR: 1.40 [1.17-1.67]). A clearer trend of poorer outcome was seen in those diagnosed postpartum (pHR: 1.84; 95% CI [1.28-2.65]) than those diagnosed during pregnancy (pHR: 1.29; 95% CI [0.74-2.24]). DFS analysis showed a significantly higher risk of relapse associated with PABC as well (pHR: 1.60 [1.19-2.16]). CONCLUSION: Our results show that PABC is independently associated with poor survival particularly those diagnosed shortly post-partum. This underscores a possible impact of the pregnant breast microenvironment on the biology and consequently the prognosis of these tumors.

Cytotoxic chemotherapy has helped improve the outcomes in patients with advanced non-small cell lung cancer (NSCLC), but we seem to have reached a plateau with respect to the benefit obtained. Also, a large subset of elderly patients and those with a poor performance status cannot tolerate these drugs at recommended doses. There is a growing need to incorporate newer drugs with different mechanisms of action and better safety profile. The epidermal growth factor receptor family (EGFR) and vascular endothelial growth factor (VEGF) have been identified as potential targets and agents acting specifically against these targets have been developed with the hope of improving outcomes. Although recent data with the small molecule EGFR tyrosine kinase inhibitors have been disappointing, there have been instances of dramatic responses thereby raising questions about the ideal patient to whom these drugs should be administered. Cetuximab, the anti-EGFR antibody has shown promising results. Bevacizumab, the anti-VEGF antibody was the first drug to demonstrate a survival benefit in first line treatment when added to chemotherapy. This review will briefly discuss the important trials using these targeted agents in advanced NSCLC.

The mammalian target of rapamycin (mTOR) is a key regulator of cell growth and proliferation. The mTOR pathway integrates signals from nutrients, energy status and extracellular growth factors to regulate many processes, including cell cycle progression, angiogenesis, ribosome biogenesis, and metabolism. Growth factors such as insulin-like growth factor, epidermal growth factor and vascular endothelial growth factor bind to and activate their corresponding tyrosine kinase receptors (TKR) located on the cell surface, to induce signal transduction to the nucleus. TKR induces intracellular signaling cascades via the phosphorylation of the phosphatidylinositol 3-kinase, which in turn phosphorylates Akt. Of particular interest among the Akt targets is the downstream effect on mTOR, which is responsible for protein synthesis of molecules necessary for nutrient uptake, angiogenesis, ribosome biogenesis, cell growth, and proliferation. Growing evidence suggests that mTOR deregulation is associated with many types of human cancer. The importance of mTOR signaling in tumor biology is now widely accepted. Consequently, a number of agents that selectively target mTOR are being developed for cancer treatment and currently temsirolimus and everolimus are approved for the treatment of advanced renal cell cancer. However, the therapeutic benefit of mTOR inhibitors in the clinic may vary depending on the activation state of the different components of the mTOR pathway in a given case. Therefore it seems clear that predicting sensitivity to rapamycins in different cancers will likely require assessing multiple molecular markers related to mTOR signaling pathway, such as phosphatase and tensin homolog (PTEN), phospho-Akt, cytoplasmic p27, and phospho-S6 kinase.

Managing pregnant patients with hematological tumors pose even more conflicts compared to solid tumors. Unlike the majority of solid tumors, hematological malignancies are potentially curable; hence it is important to deliver the best treatment options available, which sometimes could be too aggressive to deliver during pregnancy. In part II, we report the results of women with hematological malignancies treated with systemic therapies during the course of pregnancy. Lymphoma, acute leukemia and chronic myeloid leukemia were the most commonly treated. We discuss the safety of the different regimens reported and propose alternatives to standardized approaches in case they pose significant risk to the pregnancy and/or the fetus.

The association of cancer and pregnancy is increasingly encountered nowadays in clinical practice. Due to the relative rarity of the situation, it lacks a systematized approach. Different systemic therapies are used in managing cancer with uncertainty regarding the potential hazards they could pose on the pregnancy and/or the fetus. We have performed a systematic review of literature to identify all reports addressing cancer patients who were exposed to any of the known systemic therapies during the course of the pregnancy. The results were discussed in two parts; part I addresses pregnant patients with solid tumors while part I for those with hematological malignancies. In part I, we identified different solid tumors diagnosed and treated during the course of pregnancy. Breast cancer was the most commonly treated followed by ovarian cancer. Other tumors were treated as well including lung cancer, cervical cancer, sarcoma and melanomas. It is important to acknowledge the intent of therapy (palliative vs. curative) and the patients has to be properly counseled to reach an informed decision. We aim to provide a more robust consensus on how to approach these cases and provide a higher degree of evidence to support the safety of applying certain management strategies over the other.

Lung cancer in pregnancy is a rare situation; however, it is increasingly reported in the past two decades. The association might be more encountered in the coming years due to the rising trends of cigarette smoking among young women and tendency to delay pregnancy to later in life. We performed a literature search without any date or language restriction and identified 44 cases diagnosed and/or treated for lung cancer during the course of pregnancy. Patients had poor post-partum outcome with less than one-forth alive at 1 year following delivery. There was a high incidence of metastases to the products of conception reaching 26%. Eight patients were treated with systemic therapies during the course of gestation with normal fetal outcome and no evidence of fetal or placental metastases. Counseling of these patients is very important. Apart from the clinical conflict they pose, some ethical aspects should be taken in consideration. The poor maternal prognosis should be discussed and the patient's autonomy should be respected to decide whether she wants to keep the pregnancy or not.

Her-2/neu-positive tumors account for approximately 20% of all breast cancer and these tumors carry poor prognosis. Trastuzumab and lapatinib are 2 agents that have gained FDA approval for treating Her-2/neu-positive breast cancer. Trastuzumab has been shown to improve all endpoints when added to chemotherapy compared to chemotherapy alone, both in the adjuvant and metastatic phases. The addition of lapatinib to capecitabine has recently been shown to improve time to progression in trastuzumab-refractory patients with unique activity against brain metastasis. In spite of their impressive results, a significant fraction of patients still develop either primary or secondary resistance, a fact that entails the discussion of possible mechanisms of resistance. Biomarkers including PTEN, p95HER2, IGF1R and others have been linked to response to Her-2/neu-targeting agents. In this article, we overview the Her-2/neu signaling pathways and how a better understanding of the different molecular aspects of this oncogene could serve in optimizing the use of Her-2/neu-targeting agents. We also discuss the preclinical and clinical data of these biomarkers that may guide clinicians in choosing the right drug whenever possible.

Follicular dendritic cell sarcoma is a rare, malignant, non-lymphoid cell-derived tumor that originates from B-lymphoid follicles of nodal and extranodal sites. It has been reported in around 100 cases in the literature, mostly for the head and neck region. Surgery and radiotherapy were considered the mainstay of treatment for localized disease. As for the metastatic setting, classic lymphoma and sarcoma regimens were previously tested with dismal responses. Patient and Methods: In this report, we examined imatinib in combination with gemcitabine and cisplatin for treating a male patient with metastatic follicular dendritic sarcoma to the liver and lung. Results: The patient achieved complete pathological remission confirmed by positron emission tomography (PET) scan after 8 cycles. Conclusion: Our case is the first to report a role for imatinib and to show complete pathological remission in this rare disease. An imatinibbased combination could serve as a good therapeutic option for such cases.

BACKGROUND Due to the rising trend of delaying pregnancy to later in life, more women are diagnosed with breast cancer before completing their families. Therefore, enquiry into the feasibility and safety of pregnancy following breast cancer diagnosis is on the rise. Available evidence suggests that women with a history of breast cancer are frequently advised against future conception for fear that pregnancy could adversely affect their breast cancer outcome. Hence, we conducted a meta-analysis to understand the effect of pregnancy on overall survival of women with a history of breast cancer. METHODS Two of the authors independently performed a literature search up to September 2009 with no language restrictions. Eligible studies were published retrospective control-matched, population-based and hospital-based studies that have addressed the impact of pregnancy on the overall survival of women with history of breast cancer. Pooling of data was done using the random effect model. Unpublished statistics from three studies were obtained to perform further subgroup and sensitivity analyses. This included examining the effect of pregnancy according to age at diagnosis, healthy mother effect, type of study, nodal status and other parameters. RESULTS Fourteen studies were included in this meta-analysis (1244 cases and 18,145 controls). Women who got pregnant following breast cancer diagnosis had a 41% reduced risk of death compared to women who did not get pregnant [PRR: 0.59 (90% confidence interval (CI): 0.50-0.70)]. This difference was seen irrespective of the type of the study and particularly in women with history of node-negative disease. In a subgroup analysis, we compared the outcome of women with history of breast cancer who became pregnant to breast cancer patients who did not get pregnant and were known to be free of relapse. In this analysis, we did not find significant differences in survival between either group [PRR: 0.85; 95% CI: 0.53-1.35]. CONCLUSIONS This study confirms that pregnancy in women with history of breast cancer is safe and does not compromise their overall survival. Hence, breast cancer survivors should not be denied the opportunity of future conception.