Dermatological Toxicity in Women With Breast Cancer Undergoing Chemotherapy Treatment

This study aimed to analyze the occurrence of skin toxicity caused by drugs used in the protocol of neoadjuvant and adjuvant chemotherapy among women with breast cancer. Patient records of 72 women who were subject to this therapy between 2003 and 2006 were assessed. Of the 558 cycles of chemotherapy, 152 adverse events were registered. There were 37 registrations of dermatological toxicity, of those, 20 were extravasations that affected 17 women. Nine reports of hardened local injury, local fibrosis, pain, and hyperemia were registered during neoadjuvancy. In adjuvancy, among the 11 extravasations registered there were reports of hardened local injury, fibrosis and local pain. Lack of follow-up records for both periods was observed. Registration of the events and reports by the nursing team are essential to monitor the sites of venous puncture during the chemotherapy treatment, besides measuring and making a photographic record of the site.


Introduction
Antineoplastic chemotherapy or use of chemical agents, singly or in combination, has been one of the principle modes of treatment for malignant tumors.Nonetheless, the indiscriminate attack promoted by chemotherapeutic agents on cancer or normal cells generates undesirable effects, known and feared by individuals who need this type of treatment (1) .These effects are called adverse events, and include any unfavorable symptom, sign or disease, including abnormal laboratory findings, temporarily associated with the use of treatment or medical procedure (2) .
The adverse effects of chemotherapeutic drugs have varying frequencies and intensities, according to the drugs used, and can be divided into non-hematological, which include gastrointestinal, pulmonary, cardiac, hepatic, neurological, renal, bladder and dermatological Gozzo TO, Panobianco MS, Clapis MJ, Almeida AM. toxicities, reproductive disorders, metabolic alterations, allergic reactions and fatigue; and hematological, which include leukopenia, anemia, thrombocytopenia and febrile neutropenia (1) .
The adverse dermatological events occur in the tissue around the area of drug application.This group includes changes such as: phlebitis, rash, pain, erythema and tissue necrosis secondary to extravasation of vesicant drugs out of the venous bed.They may also occur systemically, alopecia being the most common, followed by less common changes such as erythema, urticaria, photosensitivity, hyperpigmentation and changes to the nails (1) .
In addition to these adverse events, extravasation may occur in the administration of the chemotherapeutics.This is a term used to describe the unintentional administration of vesicant solution or medication into areas outside of the venous system (3)(4) .The incidence of extravasation of vesicant drugs, published in the scientific literature, is 0.01 to 6.5%, but there is a possibility of underreporting of cases (1,3) .Morbidity is related to the amount of drug extravasated, its concentration, the location of extravasation, the type of device used in venous access, the conditions of health of the patient and the interval between the occurrence of the event and its recognition and treatment (3)(4) .
The extravasation of vesicant drugs causes severe irritation with vesicle formation and tissue destruction (5) , which may cause functional damage, neurological alterations, alterations in body image and, principally, the patient's loss of trust in the health professional (3) .
There are irritant drugs that, in this case, provoke cutaneous reactions of lesser intensity, such as pain and burning, but even when infused properly can cause pain and an inflammatory reaction along the blood vessel used for the infusion (1) .Also in relation to the extravasation of vesicant drugs, for each one there are procedures and antidotes that can be administered immediately after the occurrence of extravasation, through the same needle, subcutaneously around the site of extravasation, after aspiration of the highest quantity possible of the infiltrated drug.
The objective of the application of the antidotes is to limit the local inflammatory process, inactivate and remove the remaining drug and its use should be prescribed by a doctor or be defined by protocol approved by the institution (1) .Some signs and symptoms may be present immediately or several days after infusion.Immediate reactions are: burning, local discomfort and erythema, whereas later reactions include: pain, edema, induration, ulceration, vesicles, necrosis, inflammation and cellulitis (1) .
It is thought that knowledge of collateral effects and of the alternatives to control and prevent these are indispensable for the management of oncological patients.The care of patients and their families include guidance on the adverse effects related to chemotherapy and these should be based on understandable information, reinforcing the benefits of the drugs and of the alternatives for the management of the collateral effects.
This study was part of a project that evaluated the toxicity presented by women with breast cancer during that the hospital records register constitutes an important means of communication between health professionals (5) and as this was the first phase of the project it brought benefits to the design of a prospective study.

Results
Records of 72 women aged between 30 and 60 years were studied, most of them being over 45 years of age.There was a predominance of white women (83.3%) and the breast involved more frequently was the left (58%) (Table 1).During the chemotherapy, a total of 558 cycles were performed, with description of various complications that interfered in the duration of treatment.It was not possible, during the review of medical records, to identify the degree of toxicity of the non-hematologic adverse events, because the adverse events reported in the medical or nursing records were merely cited, without description, making it difficult to assess the degree of toxicity presented.
The records presented 77 registrations of adverse events during the period of neoadjuvant therapy, 18 being of hematologic toxicity and 59 of non-hematological toxicity.In the adjuvant chemotherapy 75 adverse events were recorded, 50 being of non-hematological toxicity and 25 of hematological toxicity (Table 3).
Among the non-hematologic toxicities, there were a total of 37 dermatological registrations, darkened venous pathway being prevalent in the neoadjuvant and adjuvant periods, with 23.7% and 12% respectively.
The occurrence of hardened veins was described in 10 records, divided equally between the neoadjuvant and adjuvant periods (Table 3).
Another complication observed was extravasation during the administration of chemotherapy, which occurred in 17 (23.6%)women, however, there were 20 records of extravasation, of which nine were in the neoadjuvant and 11 in the adjuvant phase.This fact shows that some women had more than one occurrence of extravasation in different cycles, or even in the same cycle (Table 4).
The IIIa clinical stage of breast cancer was observed most, with a frequency of 34.7% of the women, followed Gozzo TO, Panobianco MS, Clapis MJ, Almeida AM.The follow-up and consequences of these extravasations appear poorly reported, and there were Table 5 shows the actions related to the occurrence of extravasation.It was observed that, in spite of the protocol defined by the institution, the registrations vary regarding application with the occurrence of extravasation of the same drug, as shown below.

Discussion
Chemotherapy takes prominence in the management of tumors, and has improved the prognosis of many neoplasms, but the majority of chemotherapeutic agents can cause dermatologic toxicity.Vesicant drugs have been used routinely for decades, and there is a gap in informed evidence and in their control.When an extravasation occurs or is suspected, the infusion is stopped and the affected area should be inspected and the treatment given with the correct antidote to the drug (3)(4)6) .
The occurrence of extravasation of chemotherapy in this study (23.6%) was higher than that found in the literature, which ranges from 0.01 to 6.5% (3) , but there are few studies that report on the occurrence of extravasation.Because it is an event that can lead chemotherapy, and aims to analyze the occurrence of dermatological toxicity provoked by drugs used in the protocol of neoadjuvant and adjuvant chemotherapy among women followed in the Mastology Outpatient Clinic of the Clinical Hospital, Faculty of Medicine of Ribeirao Preto, University of Sao Paulo (HCFMRP-USP).The relevance of this is based on the fact that the institution has obtained good results with the Commitment to Hospital Quality and, seeking a seal of quality, is organizing the protocols of care.The results of this study helped with elements to the chemotherapy protocols.Methodology This study was approved by the Ethics Committee of the Clinical Hospital of the Faculty of Medicine of Ribeirao Preto, University of Sao Paulo, under number 8602/2007, along with the request for waiver of the free prior informed consent form.It was carried out at the Mastology Service of HCFMRP-USP that, during the study period, preferably used the protocol of the combination of Docetaxel 50mg/m 2 and Epirubicin 75mg/m 2 for chemotherapy in women with breast cancer in neoadjuvant treatment.For adjuvant chemotherapy, Cyclophosphamide 600mg/m 2 and Epirubicin 60mg/m 2 or other schemes were used, according to medical evaluation.For this study secondary data was used, collected from medical records of women with breast cancer, attended at the Mastology Outpatient Clinic between the years 2003 and 2006, and that underwent chemotherapy using the neoadjuvant and adjuvant regimens, already mentioned.These schemes were selected because, during the study period, they were the most frequently used.The choice of data from hospital records was based on the fact www.eerp.usp.br/rlaeRev. Latino-Am.Enfermagem 2010 Jul-Aug; 18(4):681-7.
To develop the study, a list of women undergoing chemotherapy for gynecologic cancer during the study period was first obtained from the Central Chemotherapy HCFMRP-USP.In a first review of this relationship, women undergoing chemotherapy for other types of gynecological cancer, such as cancer of the cervix and ovary were excluded.Of 404 records that were reviewed 72 were selected, of women who met the inclusion criteria: age between 30 and 60 years; chemotherapy as first treatment option, use of the neoadjuvant and adjuvant chemotherapy regimens proposed for this study; chemotherapy completed by December 2006.For data collection, an instrument was designed with information on identification data, data about the diagnosis, results of the hemograms performed before each cycle of chemotherapy, dosage of chemotherapy used in neoadjuvant and adjuvant, post-chemotherapy adverse effects, data of possible hospitalization during chemotherapy and data on the surgical procedure.
few reports recorded in the medical records, neither by the nursing staff of the Chemotherapy Center, the Mastology Outpatient Clinic or the ward in which the women with breast cancer were hospitalized.Of the 20 registrations of extravasation, it was observed that nine (45%) occurred during the neoadjuvant therapy phase and the consequences registered in medical records were: two (22.2%)reports of indurated lesion in the area, one (11.1%)reference of not presenting alterations, one (11.1%) of fibrosis in the area and one (11.1%)report of pain, hyperemia and indurated lesion at the site, while in four (44.4%) instances there is no record of the follow up action.In the adjuvant phase, of the 11 extravasations registered, two (18%) reports of indurated lesion in the area were observed and one (9.1%) of fibrosis and local pain, which was referred to physiotherapy to implement resources that improve pain and movement of the affected hand, in eight (72.7%)instances no record of the action were observed.

Table 1 -
Distribution of women undergoing chemotherapy for breast cancer by, age, color, and laterality of the tumor.Ribeirao Preto, 2008

Table 3 -
Frequency distribution of non-hematologic

Table 5 -
Distribution of women undergoing chemotherapy