in brief, the relevant point is that there is a distinction between pain and suffering. Life often brings with it pain, but suffering is existential. Pain is value neutral and can even be a positive experience. Suffering, on the other hand, requires an interpretation of pain. Thus, for example, childbirth is pain but nor suffering, for it is a happy, meaningful occasion,  whereas chronic back pain is suffering because it is purposeless and is so perceived. Consequently, as we often observe, even minor pain can lead to disproportional suffering, when it is interpreted as a meaningless and triggers hopelessness, helplessness, and loss of worth. On the other hand, suffering can be turned into… just a pain, if it can interpreted as meaningful and beneficial. This teaches us that one’s perceptions and interpretations of pain can make it  a tolerable means to some meaningful benefit, or can turn it into exquisite suffering.

If so, animals cannot suffer for they cannot judge or interpret pain. Animal rights may differ but we are talking philosophically. Sure, animals feel pain. People under anesthesia also often feel pain; their heart rate and blood pressure can be demonstrated to go up, especially when anesthesia is light, but they do not suffer because their cerebrums are turned off. The question why animals suffer pain, however,  is of a different magnitude of impact than the one of why they undergo suffering.

Two new drugs were recently approved for breast cancer, representing an important therapeutic step forward.

HALAVEN is indicated for the treatment of patients with metastatic breast cancer who have previously received at least two chemotherapeutic regimens for the treatment of metastatic disease. Prior therapy should have included an anthracycline and a taxane in either the adjuvant or metastatic setting.

This was based on an open-label, randomized, multicenter trial of 762 patients with metastatic breast cancer who received at least two chemotherapeutic regimens for the treatment of metastatic disease and experienced disease progression within 6 months of their last chemotherapeutic regimen, EMBRACE study. A statistically significant improvement in overall survival was observed in patients randomized to the Halaven arm compared to the control. An updated, unplanned survival analysis, conducted when 77% of events had been observed, was consistent with the primary analysis. In patients randomized to Halaven, the objective response rate by the RECIST criteria was 11% (95% CI: 8.6%, 14.3%) and the median response duration was 4.2 months (95% CI: 3.8, 5.0 months). The difference between overall survival in the 2 treatment groups was statistically significant; median overall survival was 13.1 months with eribulin and 10.6 months with TPC (hazard ratio, 0.81; P = .041).

This was significant but not very pronounced. The magnitude of the improvement is similar to what has been reported for docetaxel vs mitomycin plus vinblastine (31%), and for capecitabine plus docetaxel vs docetaxel alone (26%). It does not mean that Havalen is better than all other chemo choices, which remains for subsequent studies to determine, only that it is somewhat better than “any single-agent treatment (chemotherapy, hormonal or biological) or radiotherapy or symptomatic therapy alone”. Many physicians chose to use vinorelbine, gemcitabine, or capecitabine in the control arm; none chose supportive care and none used combinations.There was a prior phase II study that included patient pre-treated with anthracyclines, taxanes or capecitibine.

Xgeva(denosumab) is indicated for the prevention of skeletal-related events in patients with bone metastases from solid tumors. In the pivotal study, Denosumab was superior to zoledronic acid in delaying or preventing SREs in patients with breast cancer metastatic to bone and was generally well tolerated. With the convenience of a subcutaneous injection and no requirement for renal monitoring, denosumab represents a potential treatment option for patients with bone metastases.

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A recent review(Hickey et al, 2008) concluded: “Ultimately, the decision to take estrogen for severe menopausal symptoms should rest with the patient who is fully informed regarding the potential adverse effects on disease prognosis. A benefit of multidisciplinary care is the ability to calculate individual patient recurrence risks and to use this information in decision making about treatment choices. In addition, if endocrine therapies are producing severe menopausal symptoms with relatively small benefits in terms of recurrence or survival, the multidisciplinary (MD) team may advise that these can reasonably be stopped or adjusted. For women with advanced breast cancer, the issues of quality of life(QOL) are paramount and Hormonal Therapy may be considered following discussion with the patient”.

Tamoxifen treatment is a complicating factor. In postmenopausal women, tamoxifen acts as a weak estrogen in the ovaries, uterus, and vaginal epithelium. On the other hand, Tajima et al reported on the anti-estrogenic effects seen in the vaginal epithelium of premenopausal women being treated with tamoxifen for infertility. Tamoxifen may block systemic effects on topical estrogenic preparations.Leydenin 2008 writes: “In some cases, local estrogen can be an alternative option, although patients must be carefully monitored, and many may not be comfortable with this approach.” Cochrane Systemic Review in 2004 said: “In women with a history of breast cancer, systemic estrogen or progesterone therapy is contraindicated because of the increased risk of breast cancer recurrence. Vaginal estrogen preparations often are used to treat symptoms of vaginal atrophy in these patients because of the low levels of systemic absorption.”

Therefore, use of estrogen preparation, albeit cautiously, is a reasonable option in this situation. You might think that if estrogens are a potential problem, vaginal androgens that suppress breast cancer growth would be safer. Still using androgens is problematic from the standpoint of evidence. AndroGel is an androgen containing cream that can be used vaginally. AndroGel, an androgen, is indicated for replacement therapy in adult males for conditions associated with a deficiency or absence of endogenous testosterone, such as:

•Primary Hypogonadism (Congenital or Acquired) – testicular failure due to cryptorchidism, bilateral torsion, orchitis, vanishing testis syndrome, orchiectomy, Klinefelter’s syndrome, chemotherapy, or toxic damage from alcohol or heavy metals. These men usually have low serum testosterone levels and gonadotropins (FSH, LH) above the normal range.
•Hypogonadotropic Hypogonadism (Congenital or Acquired) – idiopathic gonadotropin or luteinizing hormone-releasing hormone (LHRH) deficiency or pituitary-hypothalamic injury from tumors, trauma, or radiation. These men have low testosterone serum levels but have gonadotropins in the normal or low range. Using it for vaginal dryness is an off-label use.

Using androgens for vaginal dryness is subject to a clinical trial: Vaginal Testosterone Cream For Atrophic Vaginitis in Women Taking Aromatase Inhibitors for Breast Cancer, NCT01122342. Results are not yet available, and I was not able to find published literature to support the safety of androgen gels for breast cancer patients. For this reason, androgen creams should for now be avoided.

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