The patient, I.L.L., is a 43 year old woman living in Cordoba, Spain, who began to have pain in the upper external quadrant of the left breast approximately 2 and a half years ago, and because of this went to see her gynaecologist, requesting that he carry out a mammogram, which was reported to be normal. Five months later, she noticed a lump in the same area. Following a further assessment by her gynaecologist, another mammogram was done, which still showed no findings suggesting malignity. A decision was taken to carry out a mammary ultrasonography which showed a nodule with a possible malignity of 2.3 x 1.4 cm in the upper exterior quadrant of the left breast. The biopsy carried out on 29th December 2002 revealed a poorly differentiated infiltrating ductal carcinoma of the breast. The oestrogen and progesterone receptors were negative, and there is no record of a study of the condition of the c-erbB-2 receptor. On 9th January 2003, an upper outer quadrantectomy was carried out in addition to a left lymphadenectomy because of an infiltrating ductal carcinoma of a maximum diameter of 22 mm, poorly differentiated (G3) associated with a high grade ductal carcinoma in situ. Of the 18 resected lymph nodes, 1 of them showed infiltration by disease (less than 2 mm). The hormonal receptors (oestrogen and progesterone) were negative. The patient was treated with adjuvant chemotherapy according to FAC x 6 cycles and external radiotherapy and began a programme of check-ups.

A year later, at the beginning of 2004, the illness recurred in the form of a small well limited nodule in the quadrantectomy scar. On 2nd February, a total mastectomy was carried out. The histopathology showed an infiltrating ductal carcinoma with a diameter of 8 mm, hormonal receptors negative, compatible with local recurrence of the previous breast cancer. The patient received no posterior treatment.

On 12th December 2004, at a routine check-up, a tumour marker value CA15.3 of 123 U/ml (reference value <35 U/ml) was detected. For this reason extension studies were carried out consisting of thoracic and abdominal CT and bone scintigraphy, detecting multiple metastases of the bone, liver and both lungs. The patient is awaiting chemotherapy treatment.

Hepatitis A in childhood with recovery ad integrum. No reference to arterial hypertension, hypercholesterolaemia, hyperuricaemia or diabetes mellitus. She has not been subjected to any surgical intervention with the exception of those related to her breast cancer.

Menarche at the age of 12. Date of last period: 2nd January 2005. She has had 2 full-term pregnancies, the first at the age of 30. She has not taken oral contraceptives.

She smoked 1 packet/day between the ages of 18 and 29. She drinks wine with some meals and does not mention the consumption of other toxic substances. She works in sales.

Analysis (10/12/04): haemoglobin: 12 g/dl. Haematocrit: 36,3%. Platelets: 325.000. Leukocytes: 6,700 (neutrophils 65%). Glycaemia: 98 mg/dl. Urea: 0.31 mg/dl. Creatinine: 0.98 mg/dl. Total bilirubin: 1.07 mg/dl. Sodium: 137 mmol/L. Potassium: 3.8 mmol/L. GOT: 17 UI/L. CPT: 25 UI/L. Alkaline phosphatase: 214 UI/L. Gamma glutamyl transferase: 260 UI/L. LDH: 430 UI/L. Cholesterol: 218 mg/dl. Triglycerides: 162 mg/dl. Proteins: 7.86 g/dl. CEA: 4.1 ng/ml. CA 15.3: 1233 U/ml.

Thoracic-abdominal CT (23/01/05): Multiple millimetre nodules in lung parenchyma in a predominantly peripheral location compatible with metastases. Liver of normal size, morphology and density with at least 4 lesions of sizes between 1 and 3 cm also of a metastatic nature. Rest of the thoracic and abdominal examination without images suggesting tumour disease.

Bone scintigraphy (18/01/05): Multiple pathological accumulations suggestive of bone metastases. Isolated accumulations can be seen in the cranial vault in the upper region of the right parietal lobe and of lesser intensity in the left parietal lobe. Heterogeneous uptake of manubrium and sternal body as well as the vertebral column in D5, D6 and L2. Intense uptake in the left sacroiliac joint and right iliopubic branch.

Echocardiogram (01/02/05): FEVI: 58%

The patient is a 43-year old woman with metastases of bones, lungs and liver from breast cancer, negative hormonal receptors, c-erbB-2 unknown.

She was previously treated using a quadrantectomy and lymphadenectomy because of an invasive ductal carcinoma with a diameter of 22 mm with 1 affected lymph node of the 18 removed. Her treatment was completed with FAC x 6 cycle scheme of chemotherapy and external radiotherapy. A year ago she presented a local relapse of 8mm, treated exclusively with a total mastectomy.

On the basis of the documents supplied, this is a middle aged woman with no significant medical history, with a current diagnosis of metastatic breast cancer. The therapeutic approach to metastatic breast cancer is to find fundamental objectives, on the one hand prolonging life and on the other that the patient enjoys a good quality of life, in so far as the applied treatments should be active and well tolerated, preventing, delaying or improving the symptoms and problems derived from such an illness. Nowadays these objectives are habitually achieved and the evolution of breast cancer with these treatments tends to be "chronic" or prolonged, instead of, in many cases, being "acute" and rapidly fatal as was the case not so many years ago. Even so, there are still cases with a rapid and mortal evolution in a relatively short period of time, despite the treatments applied.

Theoretically speaking, multiple treatments may be administered in the case of metastatic breast cancer. In this case, the most appropriate treatment is that of chemotherapy, with the purpose of treating all the areas where there is metastatic disease, while other kinds of therapy such as surgery or radiotherapy are not reasonable in that the patient has no significant symptom or problem associated with a particular metastasis. This is due to the fact that both surgery and radiotherapy are treatments that only heal a specific point where a determined tumour is found, instead of treating the whole organism, as in the case of chemotherapy.

Different basic factors must be considered when indicating the best chemotherapy treatment to be used. As well as evaluating the general condition of the patient and their organic functions (kidneys, liver, heart, etc. - apparently correct in this case -), the immunohistochemical characteristics of the tumour must be taken into account, that is to say, the molecular characteristics of the cancerous cells, which are the key to selecting the medication to be administered. Thus, for example, the fact that the tumour cells do not have hormonal receptors rules out treatment with hormone therapy medicines, which is usually very efficient and well tolerated in patients whose breast cancer shows such receptors. Nevertheless, the possibility would still exist of administering a well tolerated and active medicine, different to the classical chemotherapy, as this is specifically directed at a molecular target which is expressed in a third of breast cancers, known as "c-erbB-2" or "HER2," and an assessment of which we recommend should be carried out on the tumoural tissue of the patient (in any of the biopsies or surgeries carried out on the tumour.)

This molecular receptor of products which stimulate the growth of the cancer, in the case of being present in abnormally high quantities (overexpressed) in the cancerous cells of I.L.L. would give way to the possibility for her treatment to be based on a drug called Herceptin®¹. This is a "monoclonal antibody" that acts like a very selective "magic bullet" that specifically attacks the cells that have this overexpressed receptor (that is to say, the malignant cells) and respects the other cells of the organism. This is why it is well tolerated and works well. However, treatment with Herceptin is optimised when used in combination with chemotherapy, which, at the expense of a greater number of side effects (normally slight to moderate, and the treatment of which is usually efficient) results in a better chance of diminishing the cancer. There are different schemes or regimes that may be considered to be standard. These are generally based on the concomitant administration of Herceptin with taxanes (docetaxel or paclitaxel) or vinorelbine, which result in a very significant decrease in the extent of the illness in approximately half of these patients. Another possibility, if the general condition of the patient is good and if it is desired that the possibility of a tumoural remission be increased, is the triple combination of carboplatin, paclitaxel and Herceptin® which have been shown to be superior to the use of paclitaxel with Herceptin®². In this case the trio could be a good choice, taking into account the extent of the disease and the degree of hepatic affectation it presents, which could jeopardise the patient if an initial tumoural remission is not achieved.

On the other hand, in the case of not being able to identify the overexpression of the protein c-erbB-2 in tumour cells, there are also different chemotherapy regimes. Although the efficiency of these regimes has not been fully tested in this triple negativity situation of the molecular receptors analysed (oestrogen, progestagen and c-erbB-2 receptors) they may also result in remission, in a certain percentage of patients. In this case chemotherapy would not be combined with Herceptin®. Of the different possible combinations of potentially active chemotherapy medicines (taxanes, capecitabine, vinorelbine, platinum, etoposide, liposomal anthracyclines, etc.), the combinations of docetaxel and capecitabine³ or of paclitaxel with gemcitabine⁴ or those including platinum, are found to be amongst the most potentially active.

Chemotherapy is administered an indefinite number of cycles or times, depending on its efficiency against the cancer and the toxicity that it may produce in the patient. Normally, when a patient has undergone months of treatment, if it has been efficient, more "friendly" or bearable models of maintenance are usually tried, attempting to keep the illness under control with the maximum quality of life for the patient. It should be noted that, if these first lines of chemotherapy are not active or efficient, or, even if they are efficient, when the disease eventually becomes resistant or starts to grow again, new combinations of medication can be tried to make the disease diminish. For this, it is necessary that the patient's general condition be acceptable, the vital organs function well and she should be actively willing to fight the disease. As such, it is not unusual to see women with metastatic breast cancer who feel well and whose disease is under control a number of years, in some cases several, after having started their treatment.

Finally, with the objective of reducing the chances that, in time, the bone metastases will cause fractures, pain, etc., it would be convenient to administer bisphosphonate medicines for an undetermined time, as they have been proven to be efficient in this context of strengthening and calcifying the bone. Toxicity controls should be carried out at regular intervals. Although it is very unusual, toxicity could occur, especially in the mandible or in the kidneys⁵.

Thank you for the trust you have placed in our consultation. We are at your disposal for anything that you may need.

year 2006

Note: This Second Opinion consultation is based on the medical information and documents received, not on personal assessment of the patient by the doctor. Therefore, our Second Opinion service cannot, not does it try to, be a substitute for the medical act of assessment of the patient by his/her oncologist. It is, rather, an addition to said medical act and aims to help the patient to know more about his/her illness and the different therapeutic approaches and, in this way, assist in decisions related to the cancer.

Print

Send to a friend