Donatella Gambini

Paclitaxel-dependent prolonged and persistent complete remission four years from first recurrence of secondary breast angiosarcoma

Among angiosarcomas, radiation-induced breast sarcomas (RIBS) represent a well-known entity generally characterized by a poor outcome, especially in patients with advanced disease. Despite the unfavorable prognosis, some chemotherapeutic agents have been used to treat these malignancies, occasionally with success. Treatments with demonstrated activity against sarcomas include ifosfamide-based regimens and, more recently, taxane derivatives. We report a case of a patient having a secondary breast angiosarcoma recurring early after surgery, who achieved complete remission following treatment with weekly paclitaxel. After 4 years of maintenance therapy, with an interval between consecutive administrations of no longer than 3 weeks, the patient is still in complete remission. A locoregional recurrence was documented twice during this period, the first as a consequence of a brief treatment interruption and the second because of a treatment delay. Nonetheless, in both instances a new complete remission was rapidly achieved with the resumption of the same treatment, without evidence of any significant adverse effects. We discuss the highly unusual behavior of this malignancy and the possible role of the two different mechanisms of action of paclitaxel-antiangiogenic versus cytotoxic-depending on the schedule of administration, with evidence of false drug-resistance.

Secondary breast angiosarcoma and paclitaxel-dependent prolonged disease control: report of two cases and review of the literature.

Secondary breast angiosarcomas are a well-known entity generally characterized by a poor outcome, especially in patients with advanced disease. Among the drugs with demonstrated activity, taxane derivatives are one of the most effective histology-driven treatments against angiosarcomas. We report two cases of secondary breast angiosarcoma, both characterized by a very peculiar behavior towards paclitaxel. Both patients showed local recurrence of angiosarcoma after primary surgery, and they achieved complete remission following treatment with weekly paclitaxel. When a locoregional recurrence was observed as a result of a brief treatment interruption or a treatment delay, a new complete remission was rapidly achieved with the resumption of the drug, without evidence of any significant adverse effects.

Lymphovascular invasion and extranodal tumour extension are risk indicators of breast cancer related lymphoedema: an observational retrospective study with long-term follow-up

BackgroundBreast cancer related lymphoedema (BCRL) occurs in a substantial proportion of breast cancer survivors and is a major contributor to patients’ disability. Regrettably, there are no validated predictive biomarkers, diagnostic tools, and strong evidence-supported therapeutic strategies for BCRL. Here, we provide an integrative characterization of a large series of women with node-positive breast cancers and identify new bona fide predictors of BCRL occurrence.MethodsThree hundred thirty-two cases of surgically-treated node-positive breast cancers were retrospectively collected (2–10.2xa0years of follow-up). Among them, 62 patients developed BCRL. To identify demographic and clinicopathologic features related to BCRL, Fisher’s exact test or Chi-squared test were carried out for categorical variables; the Wilcoxon rank-sum was employed for continuous variables. Factors associated with BCRL occurrence were assessed using a Cox proportional hazards regression model.ResultsEn-bloc dissection of the axillary lymph nodes but not the type of breast surgery impacted on BCRL development. Most of BCRL patients had a Luminal A-like neoplasm. The median number of lymph nodes involved by metastatic deposits was significantly higher in BCRL compared to the control group (pu2009=u20090.04). Both peritumoral lymphovascular invasion (LVI) and extranodal extension (ENE) of the metastasis had a negative impact on BCRL-free survival (pu2009=u20090.01). Specifically, patients with LVI and left side localization harboured 4-fold higher risk of developing BCRL, while right axillary nodes metastases with ENE increased the probability of BCRL compared to ENE-negative patients.ConclusionsAssessment of LVI and ENE should be integrated with clinical and surgical data to improve BCRL risk stratification.

Remission of autoimmune hyperthyroidism after chemotherapy for cancer

Dear Editor, We report a case of autoimmune hyperthyroidism remitting after chemotherapy for breast cancer. A 44-yearold lady, with a negative personal history except for pollen allergy, showed anterior cervical swelling, palpitations, insomnia and unexplained weight decrease of 10 kg. The onset dated from almost 10 months before, but an exact diagnosis was not made until October 2011, when biochemical analyses showed free T3 = 10.6 (reference range 2.2–4.2 pg/ml), free T4 = 33 (8–17 pg/ml) and TSH 0.03 mU/l (0.28–4.3). Ultrasound scan showed hypoechoic thyroid with features of autoimmune disease; measurement of thyroid-specific antibodies gave the following results: anti-TSH receptor antibodies 5.6 U/l, anti-TPO 206 U/ml and anti-TG 1,402 U/ml. A mild leukopenia (leukocytes 4.300/mm, granulocytes 42 %) was also found. Graves’ disease was diagnosed and the patient was started on methimazole 15 mg a day; this dose was expected to control thyrotoxicosis within few months with a minimum risk of further reduction in the white cell count. Almost at the same time, a breast core biopsy revealed invasive ductal carcinoma of the breast. As clinical and instrumental staging did not reveal distant metastasis, the patient underwent quadrantectomy, but before surgical intervention, a beta-blocker was added to methimazole in order to prevent complications due to thyrotoxicosis. The definitive pathological examination showed: invasive ductal breast carcinoma, G3; estrogen receptors: positive; HER-2: negative; and Ki 67 15 %; metastases in 3 out of 30 axillary lymph nodes, with pathological staging pT2, N1 G3. According to standard guidelines, an adjuvant chemotherapy was indicated (4 courses of epirubicin– cyclophosphamide followed by 4 courses of docetaxel), followed by complementary radiotherapy and tamoxifen for 5 years. Because of a mild leukopenia at the onset and concerns about the alleged increased risk of agranulocytosis during concomitant methimazole and antineoplastic drugs, methimazole was discontinued despite thyroid function was not yet normalized, maintaining beta-blocker monotherapy. In spite of our fears, the first course of chemotherapy induced a decrease in FT3 and FT4 levels, followed by full normalization after the second course. After 4 courses, also the TSH value was in the normal range and, after the completion of chemotherapy, thyroid autoimmunity markers were nearly negativized. Tolerance to chemotherapy was quite good: mild mucositis and tardive neutropenia occurred, requiring supportive therapy with G-CSF in order to maintain the right schedule. After four courses of chemotherapy, the beta-blocker was gradually discontinued. At present, 12 months after beginning chemotherapy, the patient is clinically and biochemically euthyroid; antithyroglobulin and anti-TSH receptor antibodies remain negative, with only slightly positive anti-TPO. Table 1 lists the results of the endocrine tests over 11 months of followup and the time relationships with chemotherapy. M. Baldini (&) M. D. Cappellini U.O. Medicina Interna 1A, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Dipartimento di Medicina Interna, Università degli Studi di Milano, Milan, Italy e-mail: marina.baldini@policlinico.mi.it

Uncommon breast malignancies: presentation pattern, prognostic issue and treatment outcome in an Italian single institution experience.

AIMS AND BACKGROUNDnOften neglected by large clinical trials, patients with uncommon breast malignancies have been rarely analyzed in large series.nnnPATIENTS AND METHODSnOf 2,052 patients diagnosed with breast cancer and followed in our Institution from January 1985 to December 2009, we retrospectively collected data on those with uncommon histotypes, with the aim of investigating their presentation characteristics and treatment outcome.nnnRESULTSnRare histotypes were identified in 146 patients (7.1% of our total breast cancer population), being classified as follows: tubular carcinoma in 75 (51.4%), mucinous carcinoma in 36 (24.7%), medullary carcinoma in 25 (17.1%) and papillary carcinoma in 10 patients (6.8%). Whereas age at diagnosis was not significantly different among the diverse diagnostic groups, patients with medullary and papillary subtypes had a higher rate of lymph node involvement, similar to that of invasive ductal carcinoma. Early stage diagnosis was frequent, except for medullary carcinoma. Overall, in comparison with our invasive ductal carcinoma patients, those with rare histotypes showed a significantly lower risk of recurrence, with a hazard ratio of 0.28 (95% CI, 0.12-0.62; P = 0.002).nnnCONCLUSIONSnAccording to our analysis, patients with uncommon breast malignancies are often diagnosed at an early stage, resulting in a good prognosis with standard treatment.