What is the ideal treatment for invasive ductal carcinoma in a 53-year-old postmenopausal female?

Hi,

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I can infer that you are a 53-year-old post-menopausal woman diagnosed with screen-detected invasive ductal carcinoma. From your reports (attachments removed to protect the patient's identity), I can understand that a post-right lumpectomy and sentinel lymph node biopsy (SLNB) was done last month. The diagnosis is that there is a presence of an invasive ductal carcinoma of 0.55 inches (Grade 2). Also, estrogen receptors (ER), progesterone receptors (PR), and human epidermal growth factor receptor 2 (HER-2) are positive. Ductal carcinoma in situ (DCIS) is also present and the margins are negative. PET (Positron Emission Tomography) prior to surgery was notable for a 0.55-inch right breast mass and there was no evidence of distant disease.

You seem to have recovered well from surgery. Regarding the diagnosis and management of early-stage HER+ breast cancer, I would say that the goals of the treatment are twofold:

1. To achieve local control directed at the site of origin (you have already had a lumpectomy and should seek consultation with a radiation oncologist).
2. Systemic treatment to reduce the risk of distant recurrence.

Notably, lumpectomy plus radiation therapy (RT) has been demonstrated to be equivalent to mastectomy in terms of survival. The goal of adjuvant therapy is to reduce the risk of systemic recurrence, that is, the development of metastasis. Metastatic disease is treatable, though not curable, and therefore adjuvant therapy is delivered to reduce the risk of recurrence and mortality from metastatic disease.

The tumor has evidence of HER2 amplification, and hence I advise you that the standard of care in this setting is a combination of chemotherapy and antibody therapy (targeting the HER2 receptor). Specifically, given the small primary (under 0.78 inches) and lack of nodal involvement of the tumor, I could say the recent studies have shown that a "de-escalation" approach of Paclitaxel and Trastuzumab has demonstrated efficacy and safety. In this single-arm, multicenter study of adjuvant Paclitaxel and Trastuzumab, the 10-year breast cancer-specific survival was 98.8%. Notably, 42% of patients had stage T1c disease while only nine percent had tumors greater than 0.78 inches. Thus, you fall in the majority of cases. Additionally, the majority of patients had ER+ disease similar to you.

Now, the possible question of doubt could be whether polychemotherapy be given or should be given only if 2-dual HER2 blockade is to be considered. This is based on some ambiguity of the tumor size (0.19 inches removed with the biopsy) and the size of the lumpectomy is 0.55 inches [although the pathology report (attachments removed to protect the patient's identity) did not state the microscopic size clearly].

I would argue that her tumor was less than 0.78 inches but however, the PET scan suggested a tumor of 0.55 inches. Also, the surgical specimen suggested a size of 0.55 inches. If I add the size of the biopsy to that of the lumpectomy specimen, it would be still under 0.78 inches. Given the excellent outcome of the APT (Adjuvant Paclitaxel and Trastuzumab) trial for tumors like yours as discussed above, I would not recommend escalating therapy to polychemotherapy (Docetaxel, or Carboplatin).

Based on the phase 3 Aphinity trial, the addition of Pertuzumab to Trastuzumab demonstrated benefit only in patients with node-positive HER2-positive early-stage breast cancer. (Six-year study suggests 95% versus 94% in the Pertuzumab and placebo groups). Thus, there is no evidence to justify the routine use of dual anti-HER2 treatment for patients with node-negative or N1(mi) early breast cancer. It is also difficult to say that the addition of Pertuzumab to Trastuzumab would be equivalent to polychemotherapy. Several trials are ongoing which are examining neoadjuvant HP alone or HP or Taxol in lieu of polychemotherapy (for example, Compass HER2).

I, therefore, recommended a regimen of Paclitaxel (80 mg two weekly for 12 weeks) and Trastuzumab (loading dose of 8 mg, followed by 6 mg per two pounds every three weeks for the complete full year of Trastuzumab.

I would like to warn you about the potential side effects of this regimen, including fatigue, diarrhea, neuropathy (consider acupuncture if you develop this), infusion reaction, bone pain, infection risk, neuropathy, and pneumonitis. Furthermore, there is a rare risk of cardiotoxicity with Trastuzumab (0.5 to 1 percent); and hence, I recommend a baseline echocardiogram to assess baseline cardiac function and suggest you repeat the echocardiogram every three to six months.

If the patient has untoward side effects from Paclitaxel (like pneumonitis), one could consider Trastuzumab emtansine (T-DM1) based on the ATEMPT trial) or Vinorelbine or Herceptin as rational alternatives. The ATEMPT trial was where patients were randomized to Trastuzumab Emtansine vs. T-DM1.

Regarding the use of scalp-cooling, which is meant to reduce blood flow to hair follicles during chemotherapy administration, it restricts the exposure of hair-generating cells to cytotoxic drugs. This intervention is successful in around 50 to 60 percent of cases.

Since you are also an HR-positive breast cancer patient, you would be a candidate for endocrine therapy for at least five years. A study on aromatase inhibitors versus Tamoxifen in early breast cancer which was a patient-level meta-analysis of the randomized trials showed that the aromatase inhibitors reduce recurrence rates by about 30% (proportionately) compared with Tamoxifen while treatments differ, but not thereafter. Five years of an aromatase inhibitor reduces 10-year breast cancer mortality rates by about 15% compared with five years of Tamoxifen, hence by about 40% (proportionately) compared with no endocrine treatment.

Also, the potential adverse effects associated with aromatase inhibitors including bone demineralization, vaginal mucosal atrophy, and arthralgias have been reviewed. In contrast, Tamoxifen can promote hypercoagulability and endometrial cancer. Moreover, endocrine therapy can also reduce the incidence of new breast cancers.

I hope this helps. Do get back if you have any further queries.

Thank you.