Marta D’Alonzo

Clinical and radiological predictors of nipple-areola complex involvement in breast cancer patients

INTRODUCTION Nipple-areola sparing mastectomy (NSM) is increasingly used in patients with non-locally advanced breast carcinoma. Literature data on the preoperative assessment of the nipple-areola complex (NAC) are inconsistent. PATIENTS AND METHODS Out of 1359 patients submitted to total mastectomy between 2001 and 2010, we selected 61 patients whose pre-operative mammogram (MX) was available (MX group) and 39 patients who underwent preoperative breast magnetic resonance imaging (magnetic resonance imaging (MRI) group). The rate of NAC involvement, the value of MX and MRI to predict NAC involvement and the performance of the Schecters and Loewns algorithms for the prediction of NAC involvement were evaluated. RESULTS In the combined MX and MRI groups, NAC involvement was found in 14% of the cases. At univariate analysis, tumour stage (p value: 0.03), central tumour location (p value: 0.004), presence of NAC retraction (p value: 0.001) and tumour-NAC distance (p value: 0.006) were associated with NAC involvement, but only the latter parameter retained statistical significance at multivariate analysis (p value: 0.05). Tumour-NAC distance was a key predictor of NAC involvement, with a negative predictive value of 94% for MX and of 100% for MRI when the cut-off was set at 10mm. Overall, the performance of Schecters and Loewns algorithms was respectively lower and similar as compared to the original series. CONCLUSIONS Occult tumour involvement of the NAC is detected in a minority of breast cancer patients submitted to mastectomy. A tumour-NAC distance ≥ 10 mm by MRI may help select patients candidate to NSM.

Treatment of climacteric symptoms in survivors of gynaecological cancer

Different treatments (surgery, radiotherapy, chemotherapy) for gynaecological cancers may cause ovarian failure or increase menopausal symptoms. There is a widespread reluctance among physicians to prescribe hormone replacement therapy (HRT) to the survivors of gynaecological cancer. This review analyses the use of HRT and of alternative therapies in such women. Squamous cervical cancer is not estrogen dependent and thus HRT is not contraindicated. While a cautious approach to hormone-dependent cancer is warranted, for women treated for non-hormone-related tumours alternative treatments for menopausal symptoms should be given due consideration, as any reluctance to prescribe HRT for them has neither a biological nor a clinical basis. In studies of HRT for survivors of endometrial and ovarian cancer, for instance, no evidence of increased risk was found, although no definitive conclusions can yet be formulated. The positive effect of HRT on quality of life seems to outweigh the unfounded suspicion of an increased risk of recurrence of non-hormone-related tumours. Effective non-hormonal alternatives for vasomotor symptoms are selective serotonin reuptake inhibitors and selective serotonin-norepinephrine reuptake inhibitors.

Chemoprevention or mastectomy for women at high risk of developing breast cancer

Breast cancer (BC) is the most commonly diagnosed invasive cancer among women; in developed countries, BC occurs in one out of eight women during her lifetime. Many factors, both genetic and non-genetic, determine a womans risk of breast cancer and several mathematical models have been proposed that determine the risk. It is important to identify those at high risk, as there are now effective preventive strategies, such as chemoprevention therapy and risk-reduction surgery. Risk-reduction agents are recommended for women aged 35 years or more who are at high risk of breast cancer. Tamoxifen is presently deemed to be the agent of choice. However, raloxifene may be preferable, at least for some postmenopausal women, because of its lack of effect on the endometrium and the reduced incidence of venous thromboembolic events compared with tamoxifen. Prophylactic surgery has been widely investigated. Bilateral mastectomy decreases the risk of developing breast cancer by approximately 90% in women at moderate or high risk and in known BRCA1/2 mutation carriers. This review summarizes the recent advances in the identification of women at high risk of developing breast cancer and reports on the strategies used to prevent breast cancer; the risk-benefit balance of such preventive choices is also briefly analyzed.

Pregnancy After Breast Cancer

Receiving cancer diagnosis can be devastating for many patients but thanks to advances in cancer therapies it is not a death sentence anymore. Cancer survival rates are increasing and life after cancer is a real chance for many patients worldwide. In Europe, about one third of cancer patients have a relative 5-year survival rate greater than 80 % [1]. Similar survival rates are seen in the United States, Canada and Australia. Lower survival rates in developing countries are most likely due to late diagnosis and limited availability of up-to-date standard treatments [2, 3].

Risk-Reducing Surgery and Treatment of Menopausal Symptoms in BRCA Mutation Carriers (and Other Risk Women)

Women with a life expectancy ≥10 years and no diagnosis/history of breast cancer who are considered to be at increased risk for breast cancer should receive counseling to decrease breast cancer risk, considering lifestyle factors, therapy with risk reduction agents, and risk reduction surgery (in BRCA1/2 mutation carriers).Bilateral risk-reducing mastectomy decreases the risk of developing breast cancer by at least 90%; it should be proposed to carefully selected women at high risk for breast cancer considering BRCA1/2 or other genetic mutations and previous history of LCIS. In current practice, atypical hyperplasia is not an indication for prophylactic mastectomy.Bilateral risk-reducing salpingo-oophorectomy decreases the risk of developing ovarian and fallopian cancer by 85–95% and breast cancer by 50% in BRCA1/2 mutation carriers when performed in premenopausal age. Peritoneal washing should be performed at surgery, and pathologic assessment should include fine sectioning of the ovaries and fallopian tubes. The additional benefit of concurrent hysterectomy is not clear at the time. In women with no personal history of breast cancer, short-term HRT use does not negate the protective effect of RRSO on subsequent breast cancer risk, and it should be offered until the time of expected natural menopause.

Fertility Preservation and Pregnancy After Breast Cancer: When and How?

Around 6 % of breast cancer cases occur in women younger than 40 years; these patients show specific issues compared to older women. The effects of local and systemic treatments such as the distortion of body image, sexuality complaints, and fertility reduction have a higher impact in this population of young women. Fertility issues should be discussed before starting any type of anticancer treatment. The optimal type of fertility preservation, the endocrine treatment duration, and the effect of subsequent pregnancies on breast cancer prognosis remain research priorities. Currently, fertility preservation techniques rely on cryopreservation of embryos, cryopreservation of mature oocytes, cryopreservation of ovarian tissue and on the administration of GnRHa concomitant to chemotherapy. Advantages and disadvantages of each technique must be evaluated in each single patient. Many studies have shown that pregnancy after breast cancer does not impair the prognosis, both in ER+ and ER− patients; a protective effect of pregnancy has even been suggested. Young patients should not be undertreated to satisfy their eagerness for pregnancy; physicians should share with them all the available options for fertility preservation and the evidence about safety of pregnancy after cancer, to make a customized and informed decision.

Androgen Receptor and Breast Cancer

Androgen receptors (ARs) are frequently expressed in breast cancer (BC) cells, but their implication as a prognostic and/or predictive marker is still controversial. Preclinical studies suggest that the action of androgens is bidirectional: mainly proliferative, because circulating androgens are the precursors of estrogens, but also antiproliferative, because AR activation restrains ER activity inhibiting normal breast tissue growth. ARs play different roles at different stages of disease or in different subtypes of BC. ARs are expressed in up to 70 % of ER-positive BC and high levels of expression confer a survival advantage. Moreover, the increase of androgens that follows the blocking of androgen aromatization into estrogens by aromatase inhibitors (AIs) could contribute to their therapeutic efficacy in AR-positive cases. Up to 50 % of ER-negative BC are reported to be positive for ARs. Currently, epidemiological, clinical, and preclinical data on the role of androgens and ARs on this BC subtype are still controversial. In HER2-expressing cell lines, preclinical studies suggest that ARs have a proliferative effect, probably due to the cross talk between ARs and HER2 pathways. In conclusion, AR is an emerging target in breast cancer, with potential significance for therapeutic management of both primary and advanced disease.