Advances in Breast Cancer Treatment - 2017 and 2018

Breast cancer is the most common cancer among women. Newly developed treatment options have also significantly extended life in breast cancers that have metastasized to other organs, meaning stage 4 breast cancer. When all stages are considered together, the 5-year survival rate, described as indicating complete recovery from a cancer, has reached % 90 for breast cancer. Looking at the advances in breast cancer over the past two years that contributed to this:

Cooling the Fingertips Reduced the Side Effect of Chemotherapy-Induced Nerve Damage (March 2018)

The chemotherapy drug we use most frequently in breast cancer, both as preventive chemotherapy and for disease that has spread throughout the body (metastatic disease), is paclitaxel. Its most important side effect is numbness in the fingertips due to nerve damage (peripheral neuropathy). Although we have some drugs and methods for patients who develop this side effect (for example, acupuncture), a study demonstrated that the development of nerve damage could be prevented.

In a study evaluating 40 patients receiving weekly paclitaxel chemotherapy for breast cancer treatment, cooling the fingers and toes before, during and after chemotherapy was shown to reduce complaints of numbness in the fingertips. This emerged as an effective supportive method that makes it easier for our patients to receive treatment.

- Related topic: Chemotherapy-related hair loss can be prevented: the Dignicap scalp cooling system received FDA approval

Abemaciclib for Treating Advanced HER2-Negative, Hormone Receptor-Positive Breast Cancer (March 2018)

Abemaciclib (brand name Verzenio) is available for women with hormone receptor-positive, HER2-negative advanced (metastatic) breast cancer. It is the third targeted drug among CDK 4/6 inhibitors. Palbociclib (Ibrance) and ribociclib (Kisqali) had previously received FDA approval.

Abemaciclib entered clinical use in newly diagnosed stage 4 breast cancer patients in combination both with aromatase-inhibiting hormone treatments and with the estrogen receptor inhibitor fulvestrant , with its combined use receiving FDA approval.

In addition, a survival benefit was demonstrated in patients who had previously received hormone-suppressing therapy and chemotherapy.

- Related topic: Abemaciclib received FDA approval for initial treatment of hormone-positive stage 4 breast cancer

Ribociclib, Effective in Metastatic Breast Cancer During Menopause, Also Demonstrated Effectiveness in Premenopausal Patients (February 2018)

Ribociclib (brand name Kisqali) belongs to the CDK4/6 inhibitor group of drugs, which suppress the cell proliferation cycle. In menopausal breast cancer patients whose cancer is hormone-dependent and lacks the HER2 receptor, studies had demonstrated that combining this group of drugs with hormone-suppressing drugs contributes to survival.

700 premenopausal patients with metastatic hormone receptor-positive breast cancer were evaluated in the MONALEESA-7 trial. When these patients received ribociclib together with drugs suppressing hormone production in the ovaries, disease-free survival was observed to reach 24 months.

Having been effective during menopause, ribociclib will now also take its place in hormone-dependent, HER2-negative breast cancer in premenopausal women.

Risk of Recurrence After Five Years of Adjuvant Hormone Therapy for Breast Cancer (November 2017)

Hormonal (endocrine) therapycontinues to improve survival in women with nonmetastatic hormone receptor -positive breast cancer. However, a large meta-analysis involving 60.000 women found that the risk of breast cancer recurrence persisted for up to 15 years after a planned five-year course of hormone therapy. Recurrence risk was strongly associated with lymph node status, tumor size and tumor grade. These data confirmed earlier recommendations for high-risk patients to extend adjuvant (postoperative preventive) endocrine therapy to 10 years. They also support offering 10-year hormonal therapy as an option to low-risk patients who tolerate treatment well.

Updated Guideline on Bone-Modifying/Protective Agents for Metastatic Breast Cancer (October 2017)

When breast cancer metastasizes , bones are among the organs that should be evaluated first. The American Society of Clinical Oncology, together with Cancer Care Ontario, published an updated guideline focusing on the role of bone-modifying agents in metastatic breast cancer. The evidence emphasized that none of the currently available bone-protective drugs is superior to the others. Zoledronic acid, the best-known bone-modifying drug in cancer medicine, and its equivalents (generally called bisphosphonates ) are administered by intravenous infusion 1 time a month. This schedule was compared with administration every 3 months, with no difference in effectiveness found. In other words, less frequent administration of the bisphosphonate zoledronic acid was shown potentially not to increase the risk of skeletal events in cancer patients (e.g., fractures or paralysis due to spinal cord compression). However, given their modest pain-relieving effects, bone-modifying agents were emphasized as insufficient on their own for managing bone pain.

- Related topic: Cancer and dental treatment! What should people using bone-protective drugs watch out for?

Long-Term Disease Outcomes in Women with Breast Cancer and Sentinel Lymph Node Metastasis (October 2017)

Early-stage breast cancer does not routinely require surgical removal of all underarm (axillary) lymph nodes if there is no palpable metastatic underarm lymph node or if only one or two sentinel nodes are metastatic; this view has become more firmly established. Information from nearly 10 years of follow-up confirmed that overall survival and disease-free survival after sentinel lymph node dissection alone were not lower than after removal of all underarm lymph nodes. For this reason, destructive underarm surgical approaches (axillary dissection) should be avoided in early-stage breast cancer patients unless necessary.

Partial Breast Irradiation for Low-Risk, Early-Stage Breast Cancer (August 2017)

Partial breast irradiation (radiotherapy) refers to limited, focused radiation as a more suitable alternative to conventional whole-breast radiation therapy after breast-conserving surgery for early-stage breast cancer. In a study of women over age 50 who had undergone breast-conserving surgery for low-risk, early-stage breast cancer, more than 2000 women were randomized to whole-breast radiotherapy or partial radiotherapy. The resulting 5-year local recurrence rates were similar. For women aged 50 and older with hormone receptor-positive disease, no lymph node involvement and a tumor size ≤ 3 cm, partial breast irradiation is a reasonable alternative to whole-breast irradiation.

Adjuvant Treatment Without Anthracycline Chemotherapy for Low-Risk HER2-Negative Breast Cancer (August 2017)

Anthracyclinesare widely used in postoperative preventive (adjuvant) treatment of early-stage breast cancer, but their cardiac side effects are undesirable. In an analysis involving women with early-stage human epidermal growth factor receptor (HER2)-negative breast cancer, more than 4000 women in total, the non-anthracycline chemotherapy regimen docetaxel and cyclophosphamide was found somewhat superior to an anthracycline, cyclophosphamide and taxane-based regimen (4-year disease-free survival rates of % 88 versus % 91). However, in subgroup analysis, anthracyclines did not significantly improve outcomes compared with non-anthracycline treatment in women with low-risk, early-stage breast cancer. In conclusion, for women requiring adjuvant (postoperative preventive) treatment, docetaxel and cyclophosphamide, with a less burdensome side-effect profile, emerge as an appropriate treatment for low-risk HER2-negative breast cancer.

Bisphosphonates Do Not Protect Against Breast Cancer in Postmenopausal Women (August 2017)

Some studies had suggested that bisphosphonates, which are bone-modifying drugs, might protect against breast cancer. However, according to a large study following 64 thousand postmenopausal women for 7 years, bisphosphonates do not prevent breast cancer. Where, then, did the idea that women using bisphosphonates develop less breast cancer originate? The likely source of the association was this: women with osteoporosis used bisphosphonates more frequently, and we know that estrogen deficiency is one cause of osteoporosis. Thus, the lower incidence of breast cancer after menopause in these individuals may result from their lower estrogen levels rather than bisphosphonate use.

Breast and Ovarian Cancer Risks in BRCA Mutation Carriers (June 2017)

In a prospective study following more than 9800 women carrying BRCA mutations, the risks of developing breast and ovarian cancer by age 80 were found, for BRCA1 carriers, to be 72 and 44 percent respectively; for BRCA2 carriers, they were 69 percent and 17 percent. Women carrying inherited breast and ovarian cancer mutations such as BRCA should be educated about genetic and modifiable risk factors such as lifestyle, and referred for genetic counseling about other risk-reducing measures, such as preventive hormonal therapy and removal of the ovaries (oophorectomy).

Adjuvant Pertuzumab for HER2-Positive Breast Cancer (June 2017)

Pertuzumab (brand name Perjeta) had benefited neoadjuvant treatment for high-risk HER2-positive breast cancer, but its role in adjuvant treatment remained a question. In the phase III APHINITY trial, patients with HER2-positive breast cancer receiving adjuvant chemotherapy and trastuzumab (brand name Herceptin), more than 4800 patients in total, were divided into two arms, with pertuzumab added to one group’s treatment and placebo (a drug containing no active ingredient) to the other. After a median follow-up of 45 months, patients receiving pertuzumab had higher three-year disease-free survival rates (% 94 versus % 93). Patients with lymph node metastasis benefited most from adding pertuzumab. Based on this study, adding pertuzumab to adjuvant treatment may be recommended for women with lymph node-positive disease, or without lymph node involvement but with a tumor larger than 2 cm. However, drug cost is the most important problem here. Because there are not yet data showing an overall survival advantage, we do not think reimbursement approval will be obtained soon in our country.