Benign Brenner tumour of the ovary: CT and MRI features.

AIM: To evaluate the computed tomography (CT) and magnetic resonance imaging (MRI) features of benign Brenner tumours (BBT) of the ovary. MATERIAL AND METHODS: This was a retrospective two-centre study comprising 35 female patients with a definitive diagnosis of BBT at histology in whom CT and/or MRI examinations had been performed. Two experienced radiologists reviewed the CT and MRI features of 39 ovarian BBT retrospectively with consensus reading. The morphological appearance and size of each tumour were recorded. The presence or absence of calcifications within the solid portion was noted at CT. The reviewed characteristics at MRI included qualitative assessment of the signal intensity of the solid portion on diffusion sequence and contrast enhancement, compared to that of the myometrium. RESULTS: CT and MRI images were available for 27 and 28 lesions, respectively. Sixteen patients had both CT and MRI examinations. BBT were unilateral in 89% of patients, and 49% of lesions were solid and 51% were mixed. Calcifications were depicted at CT in 70.4% of lesions. When present, the cystic portion was multilocular in 85% of cases and corresponded to a mucinous lesion in 74% of cases. Enhancement of the solid portion at MRI was inferior or equal to that of the myometrium in 89% of cases and signal on high b-values diffusion images was deemed low or moderate in 93% of cases. CONCLUSION: The combined CT and MRI findings of a unilateral fibrous ovarian mass containing punctate calcifications often associated with a multilocular cyst suggest the diagnosis of ovarian BBT.

Multicentric neoadjuvant pilot Phase II study of cetuximab combined with docetaxel in operable triple negative breast cancer.

Systemic therapy for triple negative breast cancer (TNBC) is mostly based upon chemotherapy. Epithelial Growth Factor Receptor (EGFR) is overexpressed in around 50% of TNBC and may play a role in its pathogenesis. Consequently, we performed a multicentric pilot Phase II neoadjuvant trial of cetuximab (anti-EGFR antibody) combined with docetaxel for patients with operable, Stage II-III TNBC. Therapy consisted of weekly cetuximab (first infusion: 400 mg/m(2), then 250 mg/m(2)) combined with six cycles of docetaxel (T: 100 mg/m(2)) q.3 weeks. Subsequently, all patients underwent surgery. The primary endpoint was pathological complete response (pCR) while clinical response, toxicity and ancillary studies were secondary endpoints. Paraffin-embedded and frozen tumor samples were systematically collected in order to identify predictive biomarkers of efficacy and resistance. From a total of 35 accrued patients, 25 were assessable for pathologic response. The pCR rate was 24% [95% CI: 7.3-40.7]. Complete clinical response rate (cCR) was observed in 22% of cases. Conservative surgery was performed in 75% of patients. Toxicity, mostly cutaneous and hematologic, was manageable. The pre-therapy ratio between CD8+ and FOXP3+ tumor-infiltrating lymphocytes equal or higher than 2.75 was predictive of pCR: 43% versus 0%, p = 0.047. Cetuximab in combination with docetaxel displays a modest activity, but acceptable toxicity as neoadjuvant therapy of operable TNBC. Similarly to previous observations using panitumumab, another anti-EGFR antibody, the immune component of the tumor microenvironment may play an important role in predicting TNBC response to the neoadjuvant therapy.

15-Lipoxygenases regulate the production of chemokines in human lung macrophages.

BACKGROUND AND PURPOSE: 15-Lipoxygenase (15-LOX) activity is associated with inflammation and immune regulation. The objectives of the present study were to investigate the expression of 15-LOX-1 and 15-LOX-2 and evaluate the enzymes' roles in the polarization of human lung macrophages (LMs) in response to LPS and Th2 cytokines (IL-4/-13). EXPERIMENTAL APPROACH: LMs were isolated from patients undergoing surgery for carcinoma. The cells were cultured with a 15-LOX inhibitor (PD146176 or ML351), a COX inhibitor (indomethacin), a 5-LOX inhibitor (MK886) or vehicle and then stimulated with LPS (10 ng · mL(-1)), IL-4 (10 ng · mL(-1)) or IL-13 (50 ng · mL(-1)) for 24 h. Levels of ALOX15 (15-LOX-1) and ALOX15B (15-LOX-2) transcripts were determined by real-time quantitative PCR. Immunoassays were used to measure levels of LPS-induced cytokines (TNF-α, CCL2, CCL3, CCL4, CXCL1, CXCL8 and CXCL10) and Th2 cytokine-induced chemokines (CCL13, CCL18 and CCL22) in the culture supernatant. KEY RESULTS: Stimulation of LMs with LPS was associated with increased expression of ALOX15B, whereas stimulation with IL-4/IL-13 induced the expression of ALOX15. PD146176 and ML351 (10 µM) reduced the release of the chemokines induced by LPS and Th2 cytokines. The effects of these 15-LOX inhibitors were maintained in the presence of indomethacin and MK886. Furthermore, indomethacin revealed the inhibitory effect of PD146176 on TNF-α release. CONCLUSIONS AND IMPLICATIONS: Inhibition of the 15-LOX pathways is involved in the down-regulation of the in vitro production of chemokines in LMs. Our results suggest that the 15-LOX pathways have a role in the pathogenesis of inflammatory lung disorders and may thus constitute a potential drug target.

The role of tomosynthesis in breast cancer staging in 75 patients.

OBJECTIVES: Compare tomosynthesis to mammography, ultrasound, MRI, and histology for the detection and staging of BI-RADS 4-5 anomalies, as a function of breast composition, lesion location, size, and histology. PATIENTS AND METHODS: Seventy-five patients underwent mammography, tomosynthesis, ultrasound, and MRI. The diagnostic accuracy of the different examinations was compared. RESULTS: The sensitivities for detection were as follows: 92.5% with MRI, 79% for ultrasound, 75% for tomosynthesis, and 59.5% for mammography. Tomosynthesis improves the sensitivity of mammography (P=0.00013), but not the specificity. The detection of multifocality and multicentricity was improved, but not significantly. Tomosynthesis identified more lesions than mammography in 10% of cases and improved lesion staging irrespective of the density, but was still inferior to MRI. The detection of ductal neoplasia was superior with tomosynthesis than with mammography (P=0.016), but this was not the case with lobular cancer. The visualization of masses was improved with tomosynthesis (P=0.00012), but not microcalcifications. Tomosynthesis was capable of differentiating lesions of all sizes, but the smaller lesions were easier to see. Lesion sizes measured with tomosynthesis, excluding the spicules, concurred with histological dimensions. Spicules lead to an overestimation of the size. CONCLUSION: In our series, tomosynthesis found more lesions than mammography in 10% of patients, resulting in an adaption of the surgical plan.

Multicentric neoadjuvant phase II study of panitumumab combined with an anthracycline/taxane-based chemotherapy in operable triple-negative breast cancer: identification of biologically defined signatures predicting treatment impact.

BACKGROUND: Triple-negative breast cancer (TNBC) is a heterogeneous group of tumors for some of which the epithelial growth factor receptor (EGFR) pathway may play an important role. We investigated the efficacy and toxicity of an anti-EGFR antibody (panitumumab) combined with a standard neoadjuvant anthracycline-taxane-based chemotherapy in patients with operable, stage II-III, TNBC. PATIENTS AND METHODS: Treatment in this multicentric neoadjuvant pilot study consisted of panitumumab (9 mg/kg) for eight cycles q.3 weeks combined with four cycles of 5-fluorouracil, epidoxorubicin and cyclophosphamide (FEC100: 500/100/500 mg/m(2)) q.3 weeks, followed by four cycles of docetaxel (T: 100 mg/m(2)) q.3 weeks. Following therapy, all patients underwent surgical resection. Pathologic complete response (pCR) in assessable patients was the main end point while clinical response, toxicity and ancillary studies were secondary end points. Paraffin-embedded and frozen tumor samples were systematically collected with the aim to identify predictive biomarkers of efficacy and resistance in order to select biologically defined subpopulations for potential further clinical development of the anti-EGFR antibody. RESULTS: Sixty patients were included with 47 assessable for pathologic response. The pCR rates were 46.8% [95% confidence interval (CI): 32.5% to 61.1%] and 55.3% [95% CI: 41.1% to 69.5%] according, respectively, to Chevallier and Sataloff classifications. The complete clinical response (cCR) rate was 37.5%. Conservative surgery was carried out in 87% of cases. Toxicity was manageable. The association of high EGFR and low cytokeratin 8/18 expression in tumor cells on one hand and high density of CD8+ tumor-infiltrating lymphocytes on the other hand were significantly predictive of pCR. CONCLUSIONS: Panitumumab in combination with FEC100 followed by docetaxel appears efficacious, with acceptable toxicity, as neoadjuvant therapy of operable TNBC. Several biomarkers could help define large subsets of patients with a high probability of pCR, suggesting a potential interest to further develop this combination in biologically defined subgroups of patients with TNBC. CLINICAL TRIAL NUMBER: NCT00933517.

[Taste receptors in the lungs: interesting or anecdotal?]. / Les récepteurs du goût dans le poumon : intéressants ou anecdotiques ?

The receptors responsible for taste perception distinguish the four basic tastes : salty, sweet, bitter and umami. Among them, the bitter taste receptors (TAS2R) are G protein coupled receptors, including 25 subtypes identified in humans to date. Although the existence of endogenous agonists remains uncertain, the TAS2R receptors have the ability to recognize natural or synthetic molecules, as various molecules produced by bacteria, or caffeine, chloroquine, or erythromycin. The expression of these receptors, initially thought to be confined to the oral cavity, has recently been described in extra-oral tissues such as the gastrointestinal tract and the lungs. The effects in the lung tissue are essentially at three levels : TAS2R receptors expressed on the cilia of epithelial cells increase the cilia vibration frequency; the stimulation of TAS2R receptors expressed in bronchial smooth muscle cells leads to bronchial relaxation; while TAS2R receptors expressed on immune cells in the lung tissue, including macrophages, are involved in the modulation of the production of pro-inflammatory cytokines. In conclusion, in view of these complementary mechanisms, TAS2R receptors may become a pharmacological target of interest for the treatment of obstructive lung diseases.

Cannabinoids inhibit cholinergic contraction in human airways through prejunctional CB1 receptors.

BACKGROUND AND PURPOSE: Marijuana smoking is widespread in many countries, and the use of smoked synthetic cannabinoids is increasing. Smoking a marijuana joint leads to bronchodilation in both healthy subjects and asthmatics. The effects of Δ(9) -tetrahydrocannabinol and synthetic cannabinoids on human bronchus reactivity have not previously been investigated. Here, we sought to assess the effects of natural and synthetic cannabinoids on cholinergic bronchial contraction. EXPERIMENTAL APPROACH: Human bronchi isolated from 88 patients were suspended in an organ bath and contracted by electrical field stimulation (EFS) in the presence of the phytocannabinoid Δ(9) -tetrahydrocannabinol, the endogenous 2-arachidonoylglycerol, the synthetic dual CB1 and CB2 receptor agonists WIN55,212-2 and CP55,940, the synthetic, CB2 -receptor-selective agonist JWH-133 or the selective GPR55 agonist O-1602. The receptors involved in the response were characterized by using selective CB1 and CB2 receptor antagonists (SR141716 and SR144528 respectively). KEY RESULTS: Δ(9) -tetrahydrocannabinol, WIN55,212-2 and CP55,940 induced concentration-dependent inhibition of cholinergic contractions, with maximum inhibitions of 39, 76 and 77% respectively. JWH-133 only had an effect at high concentrations. 2-Arachidonoylglycerol and O-1602 were devoid of any effect. Only CB1 receptors were involved in the response because the effects of cannabinoids were antagonized by SR141716, but not by SR144528. The cannabinoids did not alter basal tone or contractions induced by exogenous Ach. CONCLUSIONS AND IMPLICATIONS: Activation of prejunctional CB1 receptors mediates the inhibition of EFS-evoked cholinergic contraction in human bronchus. This mechanism may explain the acute bronchodilation produced by marijuana smoking.

Prognostic value of initial tumor parameters after metastatic relapse.

Classical prognostic factors of breast cancer are correlated to disease-free survival and overall survival (OS); their precise role is less known on metastatic disease. A total of 511 breast cancer patients without initial metastasis were treated. OS was divided in time to distant recurrence and metastatic survival (MS). Age, Scarff-Bloom-Richardson (SBR) grade, hormone receptor, axillary node involvement, and Nottingham prognostic index predicted MS in univariate analysis. Multivariate analysis retained age, SBR grade, and axillary lymph node involvement as significant independent prognostic factors. Interactions are still present between initial parameters and MS. The clinician has to take into account for treatment choice.

Late lines of treatment benefit survival in metastatic breast cancer in current practice?

Metastatic breast cancer is mostly incurable. Progressively overall survival (OS) has improved but few authors have studied treatment globally versus for each line and demonstrated the interest of chemotherapy (CT) after the third line. We selected recent patients treated during the "taxane/anti-aromatase era" for each line given. 529 received CT and 383 hormonotherapy. OS was assessed; from the date of first metastasis and from Day 1 of each CT line. Median OS was 34.1 months; 226 patients received >3 lines of CT with a steady median OS for late lines, 11.4 months per line (range 10.4-12.6). Clinical benefit after the third line of CT was obtained for 29.2-36.6% of patients. CT lasted 11.7 months "on"versus 20.6 months "off" CT. These results may support the use of more than 3 CT lines; each line can contribute to a longer survival.

Intraoperative imprint cytology examination of sentinel lymph nodes after neoadjuvant chemotherapy in breast cancer patients.

BACKGROUND: Intraoperative imprint cytology (IC) is one of several accurate, proven methods to detect tumor cells in sentinel lymph nodes (SLN) from patients with operable breast cancer. In patients treated with neoadjuvant chemotherapy (NAC), studies have demonstrated the feasibility and accuracy of SLN biopsy procedure. We evaluated the validity of IC for SLN testing in patients after NAC. MATERIAL AND METHODS: Patients with infiltrating breast carcinoma receiving NAC (n = 132) were studied prospectively. At surgery, SLN biopsy followed by axillary lymph node dissection was performed. SLN were evaluated using IC in 80 of 132 patients (60%). The results of IC in the adjuvant setting (100 patients) were used for comparison. RESULTS: SLN metastases were correctly identified using IC in 58 of 80 (72%) patients. False negative results were observed in 21 patients. The sensitivity of IC testing was 38.2% and specificity 97.8%. The positive and negative predictive values (PPV and NPV) were 92.9% and 68.2%, respectively. In univariate analysis and multivariate logistic regression analysis, patients with micrometastases or isolated tumor cells in SLN have 2.3 times higher risk of a false negative IC result than patients with macrometastases in SLN (P = .00021; relative risk [RR] = 2.3; 95% confidence interval, 1.37-3.85). The non-NAC group, which contained fewer micrometastatic cases, showed better sensitivity (47.4%) and NPV (88.9%). CONCLUSION: NAC does not seem to influence the accuracy and sensitivity of IC. Variations in sensitivity are related to the proportion of cases with micrometastases and ITC, as it was also shown in chemonaive patients.

Clinicopathological factors and nomograms predicting nonsentinel lymph node metastases after neoadjuvant chemotherapy in breast cancer patients.

BACKGROUND: Studies have demonstrated the feasibility and accuracy of sentinel lymph node (SLN) biopsy after neoadjuvant chemotherapy (NAC) in breast cancer. Some SLN-positive patients have low risk of nonsentinel lymph node (non-SLN) involvement. Our goal was to determine clinicopathological factors correlating with the presence of non-SLN metastases in patients after NAC and to assess the validity of nomograms predicting additional axillary metastases. METHODS: Patients with infiltrating breast carcinoma (n = 132) were studied prospectively. All patients received NAC. At surgery, SLN biopsy followed by axillary lymph node dissection was performed. Lymphatic mapping was done using the isotope method. Fifty-one patients were SLN positive. RESULTS: In univariate analysis, tumor size (P = 0.016) and the size of SLN metastases (P = 0.0055) were significantly correlated with the presence of non-SLN metastases. In multivariate analysis, SLN macrometastases (P = 0.047) conferred significantly increased risk of non-SLN metastases. The Memorial Sloan-Kettering Cancer Center nomogram was not reliably predictive for non-SLN metastases (area under the receiver operating characteristic curve, AUC, of 0.542), whereas the MD Anderson (AUC 0.716) and Tenon scoring systems (AUC 0.778) were validated. CONCLUSION: Our results suggest that clinicopathological factors predicting non-SLN involvement in SLN-positive patients with and without NAC are essentially the same. The risk of involvement may be assessed using existing nomograms, but additional large prospective studies are needed to determine their accuracy in patients after NAC.

p53 status and efficacy of primary anthracyclines/alkylating agent-based regimen according to breast cancer molecular classes.

BACKGROUND: We hypothesized that, among molecular subclasses of breast cancer, p53 status may have a differential predictive value for the efficacy of anthracyclines/alkylating agents-based regimen. We analysed the efficacy of a preoperative combination between 5-fluorouracil, anthracyclines and cyclophosphamide according to both p53 status and molecular classification. PATIENTS AND METHODS: Oestrogen receptor (ER), progesterone receptor (PgR), human epidermal growth factor receptor 2 (HER2) expression and p53 status were determined by immunohistochemistry in 293 samples from two different centres. A logistic regression model was used for multivariate analysis of predictors for pathological complete response (pCR). RESULTS: p53 immunostaining (54%) was associated with high grade (P = 0.002) and ER negativity (P = 0.04). p53 was detected in 59% of triple-negative tumours (ER-/PgR-/HER2-, n = 120 patients). In the overall population, pCR (9.6%) was independently predicted by high tumour grade (P = 0.002) and ER/PgR/HER2 triple negativity (P = 0.0004), but not by p53 status (P = 0.12). p53 immunostaining was associated with a trend for a higher rate of pCR in triple-negative tumours [relative risk (RR) = 2.5, 95% confidence interval (CI) = 0.8-7.5, P = 0.09], but not in non-triple-negative tumours (RR = 0.73, 95% CI = 0.16-3.3, P = 0.69). CONCLUSION: p53 status may have a different predictive value for efficacy of anthracycline/alkylating agents-based regimen in each molecular subclass, a result which may explain the different results reported in literature.

Sentinel lymph node biopsy after neoadjuvant chemotherapy is accurate in breast cancer patients with a clinically negative axillary nodal status at presentation.

BACKGROUND: In breast cancer, neoadjuvant chemotherapy (NAC) is widely used in order to enable a conservative surgery. In patients treated with NAC, the use of sentinel lymph node (SLN) biopsy, which is a good predictor of the axillary nodal status in previously untreated patients, is still discussed. The aim of our study was to determine clinicopathological factors that may influence the accuracy of SLN biopsy after NAC. METHODS: Between March 2001 and December 2006, 129 patients with infiltrating breast carcinoma were studied prospectively. Preoperatively, all of them underwent NAC. At surgery, SLN biopsy followed by axillary lymph node (ALN) dissection was performed. Lymphatic mapping was done using the isotope method. RESULTS: The SLN identification rate was 93.8% (121/129). Fifty-six out of the 121 successfully mapped patients had positive ALN. Eight out of these 56 patients had tumor-free SLN (false-negative rate of 14.3%). The false-negative rate was correlated with larger tumor size (T1-T2 versus T3; P = 0.045) and positive clinical nodal status (N0 versus N1-N2; P = 0.003) before NAC. In particular, the false-negative rate was 0% (0/29) in N0 patients and 29.6% (8/27) in N1-N2 patients. Clinical and pathological responses to NAC did not influence the accuracy of SLN biopsy. CONCLUSION: Our results show that clinical nodal status is the main clinicopathological factor influencing the false-negative rate of SLN biopsy after NAC for breast cancer. SLN biopsy after NAC can predict the ALN status with a high accuracy in patients who are clinically lymph node negative at presentation.

Does survival increase in metastatic breast cancer with recently available anticancer drugs?

Metastatic breast cancer (MBC) is incurable in most cases. While multiple treatments are available, the median survival is still approximately 2 years. We planned to assess the apparent impact of taxanes and aromatase inhibitors (letrozole, anastrozole, and exemestane) on the survival of 857 MBC patients for more than 30 years. Patients classed into decades by metastatic disease onset date did not survive significantly longer in recent years. This does not exclude some marked improvements with time: 1) in the same period, the disease-free interval for MO patients increased progressively and significantly with time; 2) the overall relapse ratio in MO patients was 20% lower in the 1990-2000 decade compared with 1980-1990; 3) since 1995, treatment for metastasis has been significantly lighter with periods of chemotherapy separated by hormonotherapy or observation in the case of negative receptors. Analyzing individual therapies, availability of taxanes since 1994 did not result in a significant increase of the overall survival. Conversely, receiving hormonotherapy was an important prognostic factor of the overall survival. Three groups were classified according to hormone therapy: group 1--tamoxifen, group 2--aromatase inhibitors, group 3--a combination of tamoxifen then aromatase inhibitors. The combination of tamoxifen then aromatase inhibitors favored a survival improvement from metastasis appearance to death compared with aromatase inhibitors alone and with tamoxifen alone. The sequential treatment of tamoxifen then aromatase inhibitors is presently discussed as a possible standard when used as adjuvant treatment. This sequential effect could also constitute a valuable concept for metastatic patients.

Neoadjuvant endocrine therapy in breast cancer.

The clinical benefits of endocrine therapy for patients with hormonosensitive breast cancer are well established. For many years, five years' treatment with tamoxifen was the gold standard of adjuvant treatment. The recent development of new endocrine agents provides physicians with the opportunity to take a more effective therapeutic approach. Nevertheless, the success of neoadjuvant endocrine therapy is much more recent and less frequently reported in the literature. This article reviews the studies published on neoadjuvant endocrine treatment (tamoxifen and aromatase inhibitors). According to the literature, neoadjuvant endocrine therapy seems to be effective and well tolerated. The newer generation of aromatase inhibitors (letrozole, anastrozole, exemestane) appear to result in better overall response rates and more conservative surgery than tamoxifen. Patients with an ER Allred score of 6 and over are most likely to respond and gain clinical benefit. The optimal duration of neoadjuvant therapy has not yet been investigated in detail. These preliminary results are interesting and should be confirmed by further studies.

Tumor parameters, clinical and pathological responses, medical management, and survival through time on 710 operable breast cancers.

The aim of the current study is an analysis of tumor parameters, clinical and pathological responses, medical management, and survival on 710 operable breast cancer patients who received neoadjuvant chemotherapy from 1982 to 2004 and were grouped into four successive periods according to diagnosis date: (1) 1982-1989; (2) 1990-1994; (3) 1995-1999; and (4) 2000-2004. Patients were treated by different neoadjuvant chemotherapies combinations: AVCF/M, TNCF, NEM, NET, TAXOTERE, FEC 50, 75, 100, FAC 50, and TAXOTERE-TNCF, mainly in successive prospective phase II trials. They received a median number of six cycles (range, 1-9). After primary chemotherapy, patients underwent a surgery and a radiotherapy. In case of significant residual disease, some patients received additional courses of chemotherapy. In addition, menopausal patients with hormonal receptor-positive tumors received tamoxifen for 5 yr. Clinical factors had some remarkable variations with time. The median age of the patients was 49.5 yr (range, 26-81). The size of the tumor was significantly greater from 1995; conversely, clinical lymph-node involvement was lower in period 4 than in the first period. The percentage of invasive ductal carcinoma and of SBR III tumors increased about 20% from 1982-1989 to 2000-2004. The number of positive hormonal receptors increased from 38.3% in period 1 to 74% in period 4. The clinical response rate improved recently from before 1990. The pathological response rate was greater in periods 2 and 3 than in periods 1 and 4. An adjuvant hormonotherapy became progressively more frequently given (44.7 for period 1 and 73.3% for period 4). Finally, no significant difference was found when we compared overall and disease-free survival through the four periods. It appears that the progressive increase of tumor burden was compensated by more effective treatments.

[Therapeutic potential of melatonin in cancer treatment]. / Potentiel thérapeutique de la mélatonine dans la prise en charge de la pathologie cancéreuse.

Melatonin is a small lipophile molecule, essentially secreted by pineal gland. The synthesis of this hormone shows a circadian pattern with a peak around 2-3 hours am. Many melatonin receptors are found in the body, which explains its multiple functions as biological rhythms resynchronisation, sleep induction, vasoregulation and even immunomodulation. Many experiments realised in this field have permit to discover different interactions between melatonin and the immune system, and especially the link which exists between melatonin and the fight against cancer via the immune system. Phase II studies reported a decrease of thrombocytopenia, an increase of some cytokines rate and an increase of objective responses in cancer patients. In order to confirm these results and to lead further research, we propose to realise a phase II randomised study melatonin versus placebo in metastatic breast cancer patients after two lines of treatment.

[Stress, cancer and circadian rhythm of melatonin]. / Stress, cancer et rythme circadien de la mélatonine.

Influence of stress on immunity and pathogenesis relates to corticotropic axis: hypothalamus-hypophysis-surrenals (HHS). Its over-stimulation due to traumas during early childhood or before birth seems to generate brain abnormalities such as reduction of hippocampus volume. More typical of adult age, hypothalamus-pineal gland axis (HP), responsible for melatonin production, may be impaired because of chronic stress, mainly through sleep disturbances or addictive behaviours. Old age has been reported to produce same impairments. Circadian cycle of melatonin is closely related to immune functions and its disturbance seems to induce, among populations undergoing frequent changes of life rhythm, a significant raise of cancer incidence: night shift workers, air pilots... Stress then seems enable to increase cancer risk through its negative impact on HHS and HP axis and therefore on immunity. Immunotherapy, which was an interesting solution considering this, has not yield yet expected results. Upstream, other ways have been successfully investigated in prospective randomised trials, such as psychotherapeutic treatments, with positive effects on cellular immunity and survival. The ability to condition immune responses in animals allows thinking that hypnotherapy could also be used along with standard treatments.