Medical School 2020, Year 2, Week 17

From our anonymous insider…

Monday morning begins with an introduction to gynecology from an energetic 36-year-old Ob/Gyn. She began at the end: menopause. “Menopause occurs between 45 and 55, with the average age at 51.” She explains that hormone replacement therapy (HRT) is one of the most effective mechanisms to treat vasospasm (hot flashes) in postmenopausal women. “Estrogen is the fertilizer, progesterone is the lawn mower. Remember that. If the patient has a uterus, you must give combination [estrogen/progesterone] to thin the endometrium. If the patient underwent hysterectomy, she can just take estrogen. Nothing to grow!”

“Menopause symptoms typically last no more two years, but can last up to 13 years. Every three years we reevaluate the HRT and medications. Usually we take them off for a month and restart if needed. Some patients just feel better on HRT so they request to continue.” Birth control pills contain the identical hormones. Straight-Shooter Sally, commenting on a controversy over requiring private employer-provided health insurance to offer zero co-pay contraception: “I wish people would recognize that birth control pills are used for a lot more than just birth control.”

Particular Patrick asked why so many older women have hysterectomies [removal of the uterus]: “Hysterectomies have fallen out of favor in the past decade or so. The history of hysterectomies is fascinating, especially the regional variation. Where there were a lot of Ob/Gyns, there were a lot of hysterectomies. Same exact pattern for laminectomies [removal of part of the vertebrae to alleviate back pain]. Where there were a lot of neurosurgeons, there were a lot of laminectomies.”

In our small groups, we discussed the costs and benefits to HRT in treating menopause symptoms. Laid-back Larry, a San Francisco native with a soothing voice, presented on a Women’s Health Initiative (WHI) study on the side effects of HRT in 160,000 postmenopausal women aged 50-79. In our age of identity politics, before talking about the medical conclusions of the study, Larry delivered an encomium about Dr. Bernadine Healy, the founder of WHI and one of ten women (out of 120 students total) in the Harvard Medical School Class of 1966 and later appointed by Ronald Reagan to be director of NIH.

After we finished celebrating women overcoming gender barriers, we returned to the study per se. WHI concluded that the lowest dose of combination HRT should be used to minimize the risk of coronary artery disease and breast cancer. Larry: “For anyone who says that investment in public health is not worth it, and that we need more military spending, look at this economic analysis. The study cost $625 million. That’s five F-35 fighters.” Our facilitator asked, “So you do not think we should have the F-35 program?” Larry: “No, I do not think we should have the F-35 program or any military spending until we can get our domestic policies in order.” Larry cited “Economic return from the Women’s Health Initiative estrogen plus progestin clinical trial: a modeling study” (Annals of Internal Medicine, 2014), describing the results of an add-on $260 million study:

The WHI scenario resulted in 4.3 million fewer CHT users, 126,000 fewer breast cancer cases, 76,000 fewer cardiovascular disease cases, 263,000 more fractures [no free lunch, unfortunately], 145,000 more quality-adjusted life-years, and expenditure savings of $35.2 billion. The corresponding net economic return of the trial was $37.1 billion ($140 per dollar invested in the trial) at a willingness-to-pay level of $100,000 per quality-adjusted life-year.

The 95% CI [confidence interval] for the net economic return of the trial was $23.1 to $51.2 billion.

[Why did this cost nearly $1 billion? It is expensive to follow patients for years.]

Wednesday morning, a pathologist led a two-hour workshop on breast cancer, which 1 in 8 women will develop. Breast cancer prognosis depends on several factors:

• Type: lobular (epithelial cells that form the milk-producing lobules) or ductal (epithelial cells that form the ducts that transport the milk to the nipple).
• Stage: TNM method – Tumor size, Nodal involvement and presence of Metastasis.
• Grade: histologic characteristics of the biopsy and genetic profile on the tumor sample. If the ductal or lobular carcinoma has not invaded outside the glandular structure, the cancer is called in situ (e.g., ductal carcinoma in situ, DCIS). If the cancer cells have spread past this barrier into the connective tissue of the breast, the cancer is called invasive. Invasive ductal carcinoma classically presents with dimpling of the skin.

The easiest breast cancer to treat is estrogen-positive and her2-positive (proto-oncogene receptor). We can inhibit the estrogen signal with endocrine therapy (e.g., aromatase inhibitor or estrogen-modulator tamoxifen) and the her2 growth signal can be inhibited with trastuzumab (Herceptin, antibody against her2).

Straight-Shooter Sally: “We’re getting all the low hanging fruit. All the cancer signal is going through this bad apple. I just cannot envision us ever getting ahead of cancer with multiple aberrant cross-talking pathways like in triple-negative breast cancer. Good luck!” (Triple-negative cancer does not express estrogen receptors, progesterone receptors, or her2 receptors.)

Our patient case: Kim, a 39-year-old nonsmoker premenopausal college professor, presents for a discrete hard mass in her left breast detected on self-examination. She undergoes ultrasound-guided needle biopsy which reveals a ER+/Her2- ductal carcinoma in situ with a high risk of recurrence. She undergoes radiation followed by a mastectomy and adjuvant chemo with tamoxifen (the estrogen modulator discussed above).

Kim, now 45, is in remission after five years of tamoxifen. She came in with her surgeon, a 40-year-old who specializes in breast reconstruction.

Type-A Anita asked How has this experience changed your perspective on life? “It has not really changed my perspective. I am not someone who creates a bucket list… The main thing this diagnosis did was prevent me from adopting a child. I knew before the cancer that I would not be able to have children so my husband and I began the adoption process. The agency requires both parents be home for a random drop-in session. My husband traveled a lot for his job so he quit, taking a large pay cut. By the time we were settled, I got this breast cancer diagnosis. I remember talking to a woman at the [government-licensed] adoption agency: ‘You think we would give you a child with this gravestone over your head?’” The surgeon answered: “It’s somewhat dark and morbid, but dealing with patients has made me realize that we rarely recognize the hardships of people around us. I am not talking about just cancer, but any serious health complication.”

Kim added: “There is always light in darkness. Chemotherapy is tough. I would get up at 6:00 am to go to the chemo center and get to work by 8:30 am. After a few weeks, I was just exhausted. My husband was gone many days. I remember getting home every weekday to find a fully prepared dinner in a basket delivered by some unknown mensch. To this day I do not know if it was my church, coworker, neighbor. That helped so much.” [Kim was not Jewish, but apparently had picked up the Yiddish term mensch.]

Kim passed around her various accessories from her mastectomy. “I would wear a lot of scarves. My students must have thought I was a crazy scarf lady. I would wear scarves in the summertime to hide my mastectomy. One afternoon, my husband and I were doing yardwork and I was not wearing my special bra. The neighbors passing by would stare at me. I wanted to curl up into a ball.”

Lanky Luke asked Why did Kim go on tamoxifen instead of an aromatase inhibitor? Kim’s surgeon: “You are correct that tamoxifen has more significant side effects such as embolic events and risk of uterine cancer. However, AIs [aromatase inhibitor] are generally avoided in the premenopausal patient group because of the risk of ovarian activation [producing estrogen, which could stimulate proliferation of the breast cancer cells].”

Pinterest Penelope asked What would determine if you get a lumpectomy or radical mastectomy? “Well, radical mastectomy is a thing of the past,” Kim’s surgeon replied. “A true radical mastectomy included complete removal of the breast tissue, all axial lymph nodes, and pectoralis major muscle. What you mean is a modified radical [mastectomy] where we remove the entire breast tissue and all axial lymph nodes.” She continued, “Only in advanced stage breast cancer would we perform this. We try to preserve as many lymph nodes as possible to prevent peripheral edema in the arm. We do a sentinel lymph node biopsy where we resect a single lymph node at a time to see if there are any cancer cells. If the pathologist does not see any, we can leave the distal lymph chains. I will add that most women these days elect for a mastectomy even when a lumpectomy would give clear margins. It is very difficult to match the lumpectomy breast to the other breast.”

The surgeon explained that breast reconstruction is a two-part surgery. “The first surgery involves placing an expandable implant. We then go back a few months later to reconstruct the expanded space with a silicone implant or a saline bag. Silicone feels more realistic, but there are more side-effects compared to the saline bag. Autologous fat implants are very difficult due to preservation of the vasculature. This leads to sections of the fat graft to become necrotic, which has all sorts of complications such as infection.”

[Lawsuits regarding silicone implants in the 1980s and 1990s resulted in nearly $10 billion in awards to women who thought that they had developed diseases such as lupus and rheumatoid arthritis from these devices. Dow Corning, founded in 1943, went bankrupt as a result of these lawsuits. No scientific link was ever established, however, and silicone implants are once again on the market. (See “Panel Confirms No Major Illness Tied to Implants,” June 21, 1999, New York Times.)]

Our Ob/Gyn lecturer returned Friday for a talk on STDs, an evolving subject: “When I was in medical school, fluoroquinolones were the first line treatment for gonorrhea. When I started residency, fluoroquinolones were no longer acceptable, and we transitioned to ceftriaxone. Now we are seeing ceftriaxone is not adequate so we added azithromycin in combination with ceftriaxone. There are already macrolide-resistant [azithromycin] strains, we just hope they will not get together with ceftriaxone-resistant ones. Long term this is going to be a serious concern, especially with the rise in IUDs [because people aren’t using condoms].” She continued: “Right now we can assume someone who is treated is cured. I see that paradigm shifting in 5 or 10 years. We will need to confirm successful treatment. That is a problem when our current tests require 4 weeks to confirm cure after treatment [PCR amplification will detect DNA of dead bacterial cells]. Asking a patient to not have sex for a month is a lot more difficult than asking a patient to not have sex during the one-week treatment window.”

After learning about every kind of STD, it was time for lunch with Luke, Jane and Persevering Pete. Pete graduated college in three years and runs a small real-estate business “flipping houses” with his family who lives three hours away. He spent the last two weekends building a deck and painting the interior. He is in a long-term relationship with his college girlfriend who is an M3 at our school. Pete asks, “What is your biggest problem?” Jane responds: “Figuring out when I will do all my rotations with the Army’s constraints.” Luke: “Marriage and money.” Pete chuckles: “Marriage for me too. My girlfriend wants to get married. What do you think about marriage at our age?” Luke: “Stay away.” Pete: “I just do not think I should even consider marriage until I can envision where I will be in five years and until I am financially stable.” Jane: “You’re confusing having children with getting married.”

A handful of states had elections this week, in which Democrats generally prevailed. Students congratulated Anita on the outcome and she responded, “I feel like I can breath for the first time. Hope triumphed over fear.”

Statistics for the week… Study: 14 hours. Sleep: 6 hours/night; Fun: 1 night. Example fun: Jane visited her alma mater to celebrate the return of one classmate who has been working as an Au Pair in New Zealand for 9 months. I played soccer with classmates followed by two beers with Lanky Luke and Mischievous Mary.

More: http://fifthchance.com/MedicalSchool2020