Cutaneous metastasis occurs in about 29% of breast cancer patients and has a deep impact on patient quality of life.
A 60-year-old woman with cutaneous metastases from heavily pretreated HER2-positive breast cancer received CMFVP (oral cyclophosphamide 100 mg daily; oral prednisone 12.5 mg daily for 2 weeks, then 7.5 mg daily; intravenous weekly methotrexate 25 mg/m2, 5-5-fluorouracil 400 mg/m2 and vincristine 0.5 mg) with weekly trastuzumab and subcutaneous insulin until disease progression.
From March 2009 to November 2009 the patient was treated with the described regimen. At the best response, we observed the disappearance of some lesions and cessation of bleeding and thoracic pain. Time to progression was 8 months.
Our patient had clinical benefit from reintroduction of trastuzumab, low-dose chemotherapy and insulin. The explanation of this prolonged response is only speculative and requires further clinical confirmation in the treatment strategy of HER2-positive breast cancer.
Tumori 2016; 102(Suppl. 2): e26 - e28
Article Type: CASE REPORT
AuthorsLaura Orlando, Paola Schiavone, Nicola Calvani, Palma Fedele, Aron Goldhirsch, Saverio Cinieri
- • Accepted on 08/02/2016
- • Available online on 16/03/2016
- • Published online on 11/11/2016
This article is available as full text PDF.
Skin metastasis occurs in about 29% of breast cancer patients (1). Usually it is a manifestation of systemic disease and is associated with lesions in other nonvisceral or visceral sites. However, in some cases skin is the only involved site, thus allowing prolonged survival and multiple lines of systemic therapy. Cutaneous metastases from breast cancer have varying presentations and can appear as skin nodules, ulcers, plaques, erythematous annular patches and verrucous masses, extending to scar sites, chest wall, back, head and neck, arms, and abdomen (1). In a recent cohort study, skin metastases were reported in 8.3% of patients with HER2-positive breast cancer (2).
A 60-year-old woman with cutaneous and lymph node metastases from HER2-positive breast cancer, heavily pretreated with chemotherapy and anti-HER2 targeted therapies, experienced a surprisingly prolonged response to CMFVP (Cooper regimen) (3) combined with trastuzumab and low-dose insulin.
The patient was first diagnosed with locally advanced breast cancer in 2005, when a total left mastectomy was performed. The pathological features revealed non-endocrine-responsive disease and HER2 overexpression. She received trastuzumab plus vinorelbine, followed by trastuzumab alone. The first relapse occurred in the contralateral axilla, which was dissected. Systemic therapy with trastuzumab and capecitabine was started upon further disease progression with diffuse cutaneous metastases and involvement of the right breast. Subsequent therapies included paclitaxel, gemcitabine, metronomic chemotherapy with cyclophosphamide and methotrexate, liposomal anthracyclines, and carboplatin. All treatments were given in combination with trastuzumab. The patient also received bevacizumab in a clinical trial and lapatinib in combination with capecitabine. Progression of disease after the last lapatinib-containing regimen was characterized by bleeding and painful skin lesions on the chest wall, breast, abdomen and back (
Pretreatment skin lesions.
In March 2009 the patient started treatment with the CMFVP regimen (oral cyclophosphamide 100 mg daily; oral prednisone 12.5 mg daily for 2 weeks and then 7.5 mg daily; intravenous weekly methotrexate 25 mg/m2, 5-fluorouracil 400 mg/m2; vincristine 0.5 mg on days 1 and 8 in the first month, then once a month). The regimen was administered for 6 consecutive weeks followed by a 2-week treatment-free interval. Our patient received also weekly trastuzumab and weekly low-dose regular insulin, 5 units subcutaneously if the glycemic index was ≥95 mg/dL. After the first course (6 weekly administrations), physical examination revealed the disappearance of some lesions and complete cessation of bleeding accompanied by a progressive reduction of opioid intake. After 3 courses the extent of all lesions was clearly reduced, tumor markers decreased progressively and performance status improved (
Posttreatment skin lesions.
Cutaneous metastases from breast cancer are devastating for patients and represent a challenge for the oncologist. Our patient had been heavily pretreated, since she received 10 trastuzumab-based lines of treatment before starting the CMFVP-trastuzumab combination, achieving a clinical benefit of almost 8 months. This regimen was developed by Cooper (3) and subsequently adopted by Ayre et al (4) in association with insulin as a putative biological response modifier to enhance the anticancer drug effects. Moreover, the CMFVP regimen might be considered a metronomic schedule. In our previous small series of patients, low-dose oral metronomic cyclophosphamide and methotrexate combined with trastuzumab showed substantial activity in pretreated HER2-positive patients, also in trastuzumab-resistant disease (5).
The inclusion of low-dose insulin in our schedule was justified by its initial empiric use in chronic and oncological disease as so-called potentiation therapy (4). Intravenous administration of insulin has been shown to increase the permeability of cell membranes, allowing an increased intracellular amount of antitumor agents. The antitumor efficacy of cell entry offered by insulin-receptor-mediated endocytosis has already been tested
Some innovative drugs were not yet available when our patient was treated. Impressive data with pertuzumab as first-line therapy (9) and trastuzumab emtansine (T-DM1) in subsequent lines (10) have changed the therapeutic strategy for advanced HER2-positive breast cancer; however, treatment options after progression to multiple anti-HER2 therapies are still needed. The role of old drugs, delivered as weekly metronomic schedules in association with anti-HER2 therapy, should be taken into account for patients with advanced breast cancer.
In conclusion, our patient had significant clinical benefit from the rechallenge with trastuzumab together with low-dose chemotherapy and insulin despite progression after multiple previous lines of treatment. The role of this multimodal approach in breast cancer is only speculative and requires further clinical confirmation in the treatment sequence of HER2-positive breast cancer.
- Orlando, Laura [PubMed] [Google Scholar] 1, * Corresponding Author (firstname.lastname@example.org)
- Schiavone, Paola [PubMed] [Google Scholar] 1
- Calvani, Nicola [PubMed] [Google Scholar] 1
- Fedele, Palma [PubMed] [Google Scholar] 1
- Goldhirsch, Aron [PubMed] [Google Scholar] 2
- Cinieri, Saverio [PubMed] [Google Scholar] 1
Medical Oncology Division and Breast Unit, Antonio Perrino Hospital, Brindisi - Italy
Department of Medicine, European Institute of Oncology, Milan - Italy