3.1. Chemotherapy regimen

Several polychemotherapy regimens are accepted as adjuvant chemotherapy regimen with strong evidence in patients with early stage breast cancer. The preferred regimens vary according to characteristics of disease, patients' comorbidities, patients' preferences, age, prescribing doctor, institution, or country.

Early Breast Cancer Trialists' Collaborative Group (EBCTCG) reports a meta-analysis periodically to review the data on adjuvant treatment of breast cancer. The previous data supported the adjuvant chemotherapy particularly cyclophosphamide, methotrexate and fluorouracil (CMF), anthracyclines and taxane compared with no treatment in adjuvant setting.

Trials with CMF-treated controls revealed that standard 4 AC and standard CMF were equivalent (P = 067), but that anthracycline-based regimens with substantially higher cumulative dosage than standard 4 AC [e.g., CAF or cyclophosphamide & epirubicin & fluorouracil (CEF)] were superior to standard CMF (RR 0.78, P = 0.0004) [45]. However, NSABP B-36 randomized phase III trial compared six cycles of FEC-100 with four cycles of standard AC in pts. with T1- 3 N0 breast cancer [46]. Primary and secondary endpoint analyses at 8 years did not reveal any significant differences in DFS, OS, recurrence free interval (RFI), or distant RFI, although patients and tumor characteristics were equally distributed between the two groups (<50 years old: 40%, lumpectomy: 68%, and hormone positivity: 65%). Overall, Grade 3 and 4 expected toxicities were more frequent in the FEC arm. Thus, international guidelines excluded six cycles of FEC-100 from adjuvant breast cancer treatment recommendations.

In trials adding four separate cycles of a taxane to a fixed anthracycline-based control regimen, extending treatment duration, breast cancer mortality was reduced (RR 0.86, SE 0.04, twosided significance P = 0.0005) [45].

In all meta-analyses involving taxane-based or anthracycline-based regimens, proportional risk reductions were little affected by age, nodal status, tumor diameter or differentiation, ER status, or adjuvant tamoxifen. Hence, largely independently of age (up to at least 70 years) or the tumor characteristics currently available to us for the patients selected to be in these trials, some taxane-plus-anthracycline-based or higher-cumulative-dosage anthracycline-based regimens (not requiring stem cells) reduced breast cancer mortality about one-third.

Thus, based on these strong evidences, AC followed by a taxane (either triweekly docetaxel, paclitaxel or two weekly or weekly paclitaxel) is now usually preferred regimen in most cases in whom adjuvant chemotherapy is indicated.

Nonanthracycline-based chemotherapy regimens should be preferred in certain patients with lower risk disease (node-negative), cardiac contraindication, advanced age, previous chest wall irradiation or patients who do not accept the risks of anthracycline-based therapy. In these patients, four cycles of docetaxel and cyclophosphamide (TC) are most preferred regimen.

When adjuvant chemotherapy is indicated in HR+ HER2-negative early breast cancer, taxane is mostly added to anthracycline-based regimen based on scientific data. However, patients who cannot receive taxane due to risks of allergic reactions or peripheral neuropathy, CMF can be administered instead of anthracycline or taxane- based regimens.

Dose-dense chemotherapy plays a controversial role in the adjuvant treatment of breast cancer patients. Whereas meta-analyses persistently describe a significant superiority for dose-dense treatment, the results of large phase III trials remain contradictory [47]. Some of these trials showed important differences between the dose-dense and conventional groups regarding number of cycles, type of drug, and total dose. Other trials are accepted and interpreted as dose-dense but present a mixture of dose-dense and conventional schedules.

Goldvaser et al. performed a systemic review and meta-analysis of clinical trials in which patients with early stage breast cancer were treated with adjuvant dose-dense chemotherapy [48]. Dose-dense treatment significantly improved DFS (HR 0.85, P < 0.001) and OS (HR 0.86, P = 0.008). A significantly greater relative magnitude of benefit was observed in premenopausal women and those with nodal involvement, but there was no influence of hormone receptor status on results. Adjuvant dose-dense regimens improve breast cancer outcomes. It remains uncertain whether the observed benefit reflects the impact of dose density or the inferiority of paclitaxel every 3 weeks as a control group.

Although a direct head-to-head comparison is missing, intense dose-dense epirubicin, paclitaxel, and cyclophosphamide (iddETC) or four cycles each of dose-dense epirubicin/cyclophosphamide followed by paclitaxel are the preferred adjuvant regimens for patients at risk. Patients with four positive lymph nodes should preferentially be treated with iddETC.

However, in EBCTCG meta-analyses, information was lacking about tumor gene expression markers or quantitative immunohistochemistry that might help to predict risk, chemosensitivity, or both.


**2.1 Addictions and Psoriasis**

Association between Psoriasis and addictive disorders is a longtime suspect and several studies are supporting association of Psoriasis and alcohol, and of Psoriasis and tobacco. Association between Psoriasis and alcohol seems not to be influenced by gender and shows a dose-effect relation. The most striking link between cigarette smoking and Psoriasis has been established in Palmo-Plantar Pustulosis (PPP). This link also seems to exist for other forms of Psoriasis with a dose-effect relation.

The relationship between cigarette smoking and Psoriasis has been the subject of several studies. It was showed that cigarette smoking represents a significant risk factor for appearance of Psoriasis, especially in women, in a case about five, and it has been pointed out that risk increases with the number of cigarettes consumed per day and increases in those who smoke 20 or more daily. The risk would increase further in those who have a family history of this disease. Also for PPP seems to be a relation to cigarette smoking, with a risk factor 7.2 times higher in smokers than in non smokers. The report is based on leukocyte neutrophil counts: PPP is a neutrophilic dermatosis and cigarette smoke increases peripheral neutrophil counts and alters it in morphological and functional way.

Cigarette smoking may be involved in the high prevalence of lung and oral cancer and cardio-vascular disorders in psoriatic patients. The association between alcohol and development of plaque-type Psoriasis is complex and confusing because many of the initial studies did not control for confounding factors such as tobacco use.

There are a number of difficulties in the assessment of the correlation between Psoriasis, cigarette smoking and alcohol, and even more so in establishing a causal or etiologic relationship between the three because of several confusing factors (Meyer &al., 2008).

Alcohol-controlled studies suggest that women who are smokers have an up to 3.3-fold increased risk of developing plaque-type Psoriasis. Men who are smokers do not exhibit such an increased risk, but studies have shown that smoking more than 10 cigarettes per day by men who are Psoriasis patients may be associated with a more severe expression of disease in their extremities. In addition, smoking among both men and women who are Psoriasis patients has been shown to reduce improvement rates.

Dermatologists are not only the sentinels for early diagnosis of psoriatic arthritis, but also for metabolic complications such as dyslipidemia or diabetes. Moreover, they need to keep in mind interactions between (systemic) anti-psoriatic drugs and the co-medication of their patients as well as possible consequences of these co-medications on the course of Psoriasis (Behnam & al., 2005).

Head and Neck Psoriasis 83

involvement of the auricle but also by the involvement of external auditory canal by heaps of scales that can stamp it. Diagnosis of SeboPsoriasis, that is characterised by the presence of yellowish-white unctuous scales can be put when psoriasiform lesions are localized exclusively in seborrheic areas of the face (naso-labial fold, glabella and eyebrows, auricle and retroauricular fold) and are associated with similar lesions of the hairline and the presternal area. This clinic form, on the border between Psoriasis Vulgaris and Seborrheic Dermatitis, is considered a Psoriasis arisen on patches of Seborrheic Dermatitis because of

Family history may predispose patients to scalp Psoriasis. In an analysis of Psoriasis genes in an Icelandic patient population, 296 of 1,000 Psoriasis patients experienced onset of Psoriasis on the scalp. Cluster analysis (Karason & al., 2005) of this subset of patients determined that 198 patients fit within 79 families and determined a linkage to chromosome 10. The familial nature of Psoriasis has long been recognized with evident intra and interfamilial variability. Thirty nine individual with Psoriasis (25 men and 14 women) from 9 Tunisian unrelated multiplex families (in Tunisian population the estimated prevalence of Psoriasis is of 3%) were investigated during a study period of 1 year (Ammar & al., 2009). The common form of Psoriasis was discovered in 37 cases. The nails, the scalp, the mucous membranes were involved respectively in 21, 12 and 13 cases.

Methods used to diagnose scalp Psoriasis vary in sensitivity, reproducibility, and invasiveness. Recently has been introduced a videodermoscopy scalp Psoriasis severity index (VSCAPSI) for evaluation of scalp Psoriasis (Rossi &al., 2011). This index is particularly useful in mild and moderate forms that often are not clinically appreciable. VSCAPSI takes into account extension of the area of the scalp affected, the presence and morphology of vascular patterns, erythema and desquamation. Videodermoscopy images obtained between November 2009 to June 2010 from 900 participants with various scalp and hair disorders were reviewed for distinguishing features. During the 2010 Italian congress on Psoriasis, in order to assess the reproducibility and efficacy of the VSCAPSI, 146 dermatologists were asked to evaluate 16 videodermoscopy images of scalp Psoriasis using the VSCAPSI. Of the 900 patients, 85 new cases of scalp Psoriasis were diagnosed. The other 815 patients were found to be suffering from different scalp and hair diseases. Of 146 dermatologists, 28 did not recognize erythema, 15 desquamation and 7 the vascular patterns. The VSCAPSI provides an important tool for early diagnosis, differential diagnosis

Head and neck Psoriasis (in the form of the so-called Psoriasis vulgaris or plaque type of Psoriasis and guttate Psoriasis) commonly involves the skin surface of the scalp and the face (eyebrow, nose, upper lip, forehead, and hairline) and presents as papules, well-demarcated erythematous plaques with a scaly surface or as papulo-squamous lesions covered by fine silvery-white and loosely adherent scales. The amount and thickness of the scales is variable such are the plaques, ranging in size from few to several centimeters, with coalescence of smaller plaques into larger and sometimes fissured lesions.  Pustular forms of Psoriasis are rarely described on the

the Koebner phenomenon.

The Psoriasis was severe in 11 cases.

and follow-up and screening.

**3.1 Histology of head and neck Psoriasis: Gross findings**

The association between Psoriasis and alcoholism represents one of the major psychodermatological issues where a multidisciplinary approach (including dermatologist, psychiatrist, psychologist and others) is crucial for optimal outcome. Psoriasis is associated with an increased risk of comorbidity and mortality compared to the general population. It appears that patients with Psoriasis have a higher prevalence of metabolic disorders such as diabetes, hypertension, obesity, and hyperlipidemia, as well as a higher frequency of cigarette smoking. These concomitant diseases can complicate the treatment of Psoriasis.